Maili Lehto - Academia.edu (original) (raw)

Papers by Maili Lehto

Research paper thumbnail of Reply

Research paper thumbnail of Defective autologous mixed leukocyte reaction in newly diagnosed type 1 diabetes mellitus

Clinical & Experimental Immunology

We studied autologous mixed leukocyte reaction (AMLR) in type 1 (insulin-dependent) diabetes mell... more We studied autologous mixed leukocyte reaction (AMLR) in type 1 (insulin-dependent) diabetes mellitus (IDDM) patients, their healthy siblings and healthy schoolchildren, Blood samples from the patients were drawn within 1 week after hospitalization and 2 months later. AMLR was significantly depressed in the patients when compared to healthy siblings or other healthy controls. In addition, the mean AMLR responsiveness of the healthy control group exceeded that of healthy siblings. The production of IL-2 in AMLR was impaired in the patient group and the defective AMLR could be restored by addition of exogenous IL-2 in 7-10 patient cultures. However, in 3-10 patients addition of IL-2 induced no enhancement of proliferation. While the patients in general had raised levels of activated T lymphocytes these three patients had higher numbers of activated T cells than other patients. Defective AMLR and presence of activated T cells may be related and may play a role in the pathogenesis of IDDM.

Research paper thumbnail of BACTERIA ARE POLYCLONAL T-DEPENDENT STIMULANTS OF IMMUNOGLOBULIN FORMATION

Acta Pathologica Microbiologica Scandinavica Series C: Immunology, 1986

Various gram-positive and gram-negative bacteria were tested for their ability to induce antibody... more Various gram-positive and gram-negative bacteria were tested for their ability to induce antibody secretion in human blood cell cultures. Total and specific immunoglobulin levels in the culture supernatants were quantitated with enzyme-linked immunosorbent assays (ELISA). All the twelve strains used stimulated IgM and IgG secretion in adult mononuclear cell cultures. With the four strains tested, also umbilical cord blood cells produced IgM. Specific antibodies directed against two bacteria were sought in adult and newborn cell culture but none were found. Bacterium-induced antibody synthesis thus seemed to be polyclonal. Experiments with purified T and B lymphocytes showed that bacterium-driven antibody formation was T-cell dependent.

Research paper thumbnail of Sensitization to nickel from stainless steel ear-piercing kits

Research paper thumbnail of Acinetobacter species in the skin microbiota protects from allergic sensitization and inflammation

Data Revues 00916749 Unassign S0091674914011178, Sep 24, 2014

Background: The human commensal microbiota interacts in a complex manner with the immune system, ... more Background: The human commensal microbiota interacts in a complex manner with the immune system, and the outcome of these interactions might depend on the immune status of the subject. Objective: Previous studies have suggested a strong allergy-protective effect for Gammaproteobacteria. Here we analyze the skin microbiota, allergic sensitization (atopy), and immune function in a cohort of adolescents, as well as the influence of Acinetobacter species on immune responses in vitro and in vivo. Methods: The skin microbiota of the study subjects was identified by using 16S rRNA sequencing. PBMCs were analyzed for baseline and allergen-stimulated mRNA expression. In in vitro assays human monocyte-derived dendritic cells and primary keratinocytes were incubated with Acinetobacter lwoffii. Finally, in in vivo experiments mice were injected intradermally with A lwoffii during the sensitization phase of the asthma protocol, followed by readout of inflammatory parameters.

Research paper thumbnail of Räsänen, L., Lehto, M., Jokinen, I. & Leinikki, P. Polyclonal antibody formation of human lymphocytes to bacterial components. Immunology 58, 577-581

Immunology

The capacity of various bacterial components to induce antibody formation in human lymphocyte cul... more The capacity of various bacterial components to induce antibody formation in human lymphocyte cultures was studied in the present investigation. Antibody levels were determined by an enzyme-linked immunosorbent assay (ELISA). Lipopolysaccharide (LPS), bacterial cell walls (CW, isolated from Bacillus subtilis and Staphylococcus aureus Wood 46) and peptidoglycans (PG) appeared to stimulate IgM, IgG and IgA secretion, whereas lysozyme-solubilized PG and teichoic acids (TA) were ineffective. Also, umbilical cord blood lymphocytes produced IgM after stimulation with LPS, CW and PG. Coculture experiments with purified lymphocytes and monocytes indicated that B-cell differentiation was dependent on both T cells and monocytes, and that T-cell derived factors could derived factors could partially substitute for T cells.

Research paper thumbnail of Polyclonal response of human lymphocytes to Chlamydia trachomatis

Infection and Immunity

The mitogenicity of Chlamydia trachomatis was investigated. Umbilical cord blood cells from healt... more The mitogenicity of Chlamydia trachomatis was investigated. Umbilical cord blood cells from healthy newborns were used. These cells were stimulated in cultures with partially purified C. trachomatis elementary bodies. Proliferation of cultured lymphocytes and secreted immunoglobulins and leukocyte migration inhibitory factor were measured in the culture supernatants. Our results showed that C. trachomatis is able to elicit polyclonal antibody, lymphokine, and DNA synthesis.

Research paper thumbnail of Concentrations of tumor-associated trypsin inhibitor and C-reactive protein in serum in acute pelvic inflammatory disease

Clinical Chemistry

We measured tumor-associated trypsin inhibitor (TATI) and C-reactive protein (CRP) in serum of 29... more We measured tumor-associated trypsin inhibitor (TATI) and C-reactive protein (CRP) in serum of 29 patients with proven pelvic inflammatory disease (PID). TATI values were increased in seven (24%), paralleling increases in CRP. TATI was increased by about 3.5-fold in seven of eight patients with CRP concentrations greater than 90 mg/L, but in none of 21 patients with CRP concentrations less than 90 mg/L. TATI concentration and severity of PID as determined by laparoscopy or endometrial biopsy were not correlated. These results suggest that, in severe infections, regulation of TATI synthesis resembles that of acute-phase proteins.

Research paper thumbnail of Enrichment of dendritic cells from human peripheral blood

Journal of Leukocyte Biology

A simplified method is described for purification of dendritic cells from human peripheral blood.... more A simplified method is described for purification of dendritic cells from human peripheral blood. The method is based on depletion of phagocytes with carbonyl iron and magnet, followed by centrifugation of nonphagocytic cells on Percoll and elimination of contaminating T lymphocytes, B lymphocytes, natural killer cells, and monocytes from the low-density cell fraction by treatment with monoclonal antibodies and complement. The purity of enriched dendritic cells was about 80% and these cells represented 0.2% of the starting mononuclear cell population. Dendritic cells were potent autologous and allogeneic stimulators in mixed leukocyte cultures.

Research paper thumbnail of Negligible respiratory irritation and inflammation potency of pigmentary TiO 2 in mice

Inhalation Toxicology, 2015

Titanium dioxide (TiO2) is manufactured in millions of tons yearly, and it is used widely as pigm... more Titanium dioxide (TiO2) is manufactured in millions of tons yearly, and it is used widely as pigment in various applications. Until recently, TiO2 was considered toxicologically harmless and without adverse health effects. In this study, respiratory irritation and inflammation potencies of commercially available pigmentary TiO2 particles (<5 µm, rutile) were studied. Single head-only exposures (30 min) of male Crl:OF1 mice at mass concentrations 6, 11, 21, and 37 mg/m(3), and repeated exposures (altogether 16 h, 1 h/day, 4 days/week for 4 weeks) of female BALB/c/Sca mice at mass concentration of 16 mg/m(3) to pigmentary TiO2 were conducted. Minor sensory irritation was observed during acute and repeated exposures seen as elongation of the break after the inhalation, which is typical in sensory irritation, and caused by closure of the glottis inhibiting airflow from the lungs after inspiration. No pulmonary irritation, airflow limitation, nasal or pulmonary inflammation was observed. In conclusion, the respiratory irritation and inflammation potencies of the studied pigmentary TiO2 particles seemed to be low and thus can serve as an ideal control exposure agent in short-term studies in mice.

Research paper thumbnail of Topically applied ZnO nanoparticles suppress allergen induced skin inflammation but induce vigorous IgE production in the atopic dermatitis mouse model

Particle and Fibre Toxicology

Background Metal oxide nanoparticles such as ZnO are used in sunscreens as they improve their opt... more Background Metal oxide nanoparticles such as ZnO are used in sunscreens as they improve their optical properties against the UV-light that causes dermal damage and skin cancer. However, the hazardous properties of the particles used as UV-filters in the sunscreens and applied to the skin have remained uncharacterized.Methods Here we investigated whether different sized ZnO particles would be able to penetrate injured skin and injured allergic skin in the mouse atopic dermatitis model after repeated topical application of ZnO particles. Nano-sized ZnO (nZnO) and bulk-sized ZnO (bZnO) were applied to mechanically damaged mouse skin with or without allergen/superantigen sensitization. Allergen/superantigen sensitization evokes local inflammation and allergy in the skin and is used as a disease model of atopic dermatitis (AD).ResultsOur results demonstrate that only nZnO is able to reach into the deep layers of the allergic skin whereas bZnO stays in the upper layers of both damaged and...

Research paper thumbnail of Invariant Natural Killer T Cells Play a Role in Chemotaxis, Complement Activation and Mucus Production in a Mouse Model of Airway Hyperreactivity and Inflammation

PLOS ONE, 2015

CD1d-restricted invariant natural killer T (iNKT) cells play a critical role in the induction of ... more CD1d-restricted invariant natural killer T (iNKT) cells play a critical role in the induction of airway hyperreactivity (AHR). After intranasal alpha-galactosylceramide (α-GalCer) administration, bronchoalveolar lavage fluid (BALF) proteins from mouse lung were resolved by two-dimensional differential gel electrophoresis (2D-DIGE), and identified by tandem mass spectroscopy. A lack of iNKT cells prevented the development of airway responses including AHR, neutrophilia and the production of the proinflammatory cytokines in lungs. Differentially abundant proteins in the BALF proteome of α-GalCer-treated wild type mice included lungkine (CXCL15), pulmonary surfactant-associated protein D (SFTPD), calciumactivated chloride channel regulator 1 (CLCA1), fragments of complement 3, chitinase 3like proteins 1 (CH3LI) and 3 (CH3L3) and neutrophil gelatinase-associated lipocalin (NGAL). These proteins may contribute to iNKT regulated AHR via several mechanisms: altering leukocyte chemotaxis, increasing airway mucus production and possibly via complement activation.

Research paper thumbnail of A single aspiration of rod-like carbon nanotubes induces asbestos-like pulmonary inflammation mediated in part by the IL-1R

Toxicological Sciences, 2015

Carbon nanotubes (CNT) have been eagerly studied because of their multiple applications in produc... more Carbon nanotubes (CNT) have been eagerly studied because of their multiple applications in product development, and potential risks on health. We investigated the difference of two different CNT and asbestos in inducing pro-inflammatory reactions in C57BL/6 mice after single pharyngeal aspiration exposure. We used long tangled, and long rod-like CNT as well as crocidolite asbestos at a dose of 10 or 40 µg/mouse. The mice were sacrificed 4 and 16 hours or 7, 14 and 28 days after the exposure. To find out the importance of a major inflammatory marker IL-1β in CNT induced pulmonary inflammation, we used etanercept and anakinra as antagonists as well as IL1R-/- mice. The results showed that rod-like CNT, and asbestos in lesser extent, induced strong pulmonary neutrophilia accompanied by the pro-inflammatory cytokines and chemokines 16 h after the exposure. Seven days after the exposure neutrophilia had essentially disappeared but strong pulmonary eosinophilia peaked in rod-like CNT and asbestos exposed groups. After 28 days, pulmonary granulomas, goblet cell hyperplasia and Charcot-Leyden-like crystals containing acidophilic macrophages were observed especially in rod-like CNT exposed mice. IL-1R-/- mice and antagonists treated mice exhibited a significant decrease in neutrophilia and mRNA levels of pro-inflammatory cytokines at 16 h. However, rod-like CNT induced Th2 type inflammation evidenced by the expression of IL-13 and mucus production, was unaffected in IL-1R-/- mice at 28 days. This study provides knowledge about the pulmonary effects induced by a single exposure to the CNT and contributes to hazard assessment of carbon nanomaterials upon airway exposure.

Research paper thumbnail of Co-exposure with fullerene may strengthen health effects of organic industrial chemicals

PloS one, 2014

In vitro toxicological studies together with atomistic molecular dynamics simulations show that o... more In vitro toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C60 fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, m-cresol, and toluene which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolized in workplace air. Unfiltered and filtered mixtures of C60 and organic chemicals represent different co-exposure scenarios in in vitro studies where acute cytotoxicity and immunotoxicity of C60 and organic chemicals are tested together and alone by using human THP-1-derived macrophages. Statistically significant co-effects are observed for an unfiltered mixture of benzaldehyde and C60 that is more cytotoxic than benzaldehyde alone, and for a filtered mixture of m-cresol and C60 that is sligh...

Research paper thumbnail of Immediate and delayed hypersensitivity reactions to birch pollen in patients with atopic dermatitis

Acta dermato-venereologica, 1992

We investigated immediate and delayed hypersensitivity to birch pollen in 10 patients with atopic... more We investigated immediate and delayed hypersensitivity to birch pollen in 10 patients with atopic dermatitis (AD) who had experienced a worsening of their eczema during the birch pollen season. The patients were prick- and patch-tested and antigen-induced basophil histamine release and lymphocyte proliferation were measured. 9/10 birch pollen-allergic patients proved positive in the histamine release test and the results correlated with specific IgE levels measured by RAST. Birch pollen antigen induced lymphocyte proliferation in 6/10 patients, but a positive patch test result was obtained in only one case. Both peripheral blood monocytes and purified epidermal Langerhans' cells were able to present birch pollen antigen to T cells, although Langerhans' s cells seemed to function less efficiently in this respect.

Research paper thumbnail of Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans

Epidemiological studies have shown that short or insufficient sleep is associated with increased ... more Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complemented with pathway and transcription factor analysis. Expression levels of the ten most up-regulated and ten most down-regulated transcripts were correlated with subjective assessment of insufficient sleep in a population cohort (N = 472). Experimental sleep restriction altered the expression of 117 genes. Eight of the 25 most up-regulated transcripts were related to immune function. Accordingly, fifteen of the 25 most up-regulated Gene Ontology pathways were also related to immune function, including those for B cell activation, interleukin 8 production, and NF-κB signaling (P<0.005). Of the ten most up-regulated genes, expression of STX16 correlated negatively with self-reported insufficient sleep in a population sample, while three other genes showed tendency for positive correlation. Of the ten most down-regulated genes, TBX21 and LGR6 correlated negatively and TGFBR3 positively with insufficient sleep. Partial sleep restriction affects the regulation of signaling pathways related to the immune system. Some of these changes appear to be long-lasting and may at least partly explain how prolonged sleep restriction can contribute to inflammation-associated pathological states, such as cardiometabolic diseases.

Research paper thumbnail of Changed numbers of circulating immune cells after cumulative partial sleep deprivation and subsequent recovery sleep

Research paper thumbnail of CELL-MEDIATED AND HUMORAL IMMUNITY TO MUMPS VIRUS ANTIGEN

Acta Pathologica Microbiologica Scandinavica Series C: Immunology, 1986

Cell-mediated and humoral immunity to mumps virus antigen. Acta path. microbiol. immunol. scand. ... more Cell-mediated and humoral immunity to mumps virus antigen. Acta path. microbiol. immunol. scand. Sect. C. 94: 201-206, 1986. In the present study, cell-mediated and humoral immunity to mumps virus was investigated. The study population consisted of 25 subjects of whom 17 were initially seropositive for mumps. Serum antibody levels and lymphocyte blast transformation activity were measured before and after vaccination with inactivated vaccine. In addition, the subjects were skin tested and HLA-typed. Significant antibody responses, measured by enzyme-linked immunosorbent assay (ELSA), were observed after vaccination in all immunoglobulin classes. However, the elevation in antibody levels was usually transient in both seronegative and seropositive subjects. The IgA response was significantly higher in the seropositive than in the seronegative group, but no such difference was found in IgM or IgG antibodies. Vaccination also caused a significant but transient rise in lymphocyte blast transformation activity. Transformation results parallelled skin-test results and seropositivity, but not antibody levels, in the seropositive group. Pronounced IgA reactivity was significantly associated with Dw3 and Dw4 (DR3 and DR4) antigens. No HLA association was observed in IgG or IgM levels or in transformation activity.

Research paper thumbnail of SUPPRESSION OF AUTOLOGOUS MIXED LEUKOCYTE REACTION IN TYPE-1 DIABETES-MELLITUS BY INVIVO-ACTIVATED T LYMPHOCYTES

Clinical Immunology and Immunopathology, 1989

Research paper thumbnail of Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation

The Journal of allergy and clinical immunology, 2014

The human commensal microbiota interacts in a complex manner with the immune system, and the outc... more The human commensal microbiota interacts in a complex manner with the immune system, and the outcome of these interactions might depend on the immune status of the subject. Previous studies have suggested a strong allergy-protective effect for Gammaproteobacteria. Here we analyze the skin microbiota, allergic sensitization (atopy), and immune function in a cohort of adolescents, as well as the influence of Acinetobacter species on immune responses in vitro and in vivo. The skin microbiota of the study subjects was identified by using 16S rRNA sequencing. PBMCs were analyzed for baseline and allergen-stimulated mRNA expression. In in vitro assays human monocyte-derived dendritic cells and primary keratinocytes were incubated with Acinetobacter lwoffii. Finally, in in vivo experiments mice were injected intradermally with A lwoffii during the sensitization phase of the asthma protocol, followed by readout of inflammatory parameters. In healthy subjects, but not in atopic ones, the rel...

Research paper thumbnail of Reply

Research paper thumbnail of Defective autologous mixed leukocyte reaction in newly diagnosed type 1 diabetes mellitus

Clinical & Experimental Immunology

We studied autologous mixed leukocyte reaction (AMLR) in type 1 (insulin-dependent) diabetes mell... more We studied autologous mixed leukocyte reaction (AMLR) in type 1 (insulin-dependent) diabetes mellitus (IDDM) patients, their healthy siblings and healthy schoolchildren, Blood samples from the patients were drawn within 1 week after hospitalization and 2 months later. AMLR was significantly depressed in the patients when compared to healthy siblings or other healthy controls. In addition, the mean AMLR responsiveness of the healthy control group exceeded that of healthy siblings. The production of IL-2 in AMLR was impaired in the patient group and the defective AMLR could be restored by addition of exogenous IL-2 in 7-10 patient cultures. However, in 3-10 patients addition of IL-2 induced no enhancement of proliferation. While the patients in general had raised levels of activated T lymphocytes these three patients had higher numbers of activated T cells than other patients. Defective AMLR and presence of activated T cells may be related and may play a role in the pathogenesis of IDDM.

Research paper thumbnail of BACTERIA ARE POLYCLONAL T-DEPENDENT STIMULANTS OF IMMUNOGLOBULIN FORMATION

Acta Pathologica Microbiologica Scandinavica Series C: Immunology, 1986

Various gram-positive and gram-negative bacteria were tested for their ability to induce antibody... more Various gram-positive and gram-negative bacteria were tested for their ability to induce antibody secretion in human blood cell cultures. Total and specific immunoglobulin levels in the culture supernatants were quantitated with enzyme-linked immunosorbent assays (ELISA). All the twelve strains used stimulated IgM and IgG secretion in adult mononuclear cell cultures. With the four strains tested, also umbilical cord blood cells produced IgM. Specific antibodies directed against two bacteria were sought in adult and newborn cell culture but none were found. Bacterium-induced antibody synthesis thus seemed to be polyclonal. Experiments with purified T and B lymphocytes showed that bacterium-driven antibody formation was T-cell dependent.

Research paper thumbnail of Sensitization to nickel from stainless steel ear-piercing kits

Research paper thumbnail of Acinetobacter species in the skin microbiota protects from allergic sensitization and inflammation

Data Revues 00916749 Unassign S0091674914011178, Sep 24, 2014

Background: The human commensal microbiota interacts in a complex manner with the immune system, ... more Background: The human commensal microbiota interacts in a complex manner with the immune system, and the outcome of these interactions might depend on the immune status of the subject. Objective: Previous studies have suggested a strong allergy-protective effect for Gammaproteobacteria. Here we analyze the skin microbiota, allergic sensitization (atopy), and immune function in a cohort of adolescents, as well as the influence of Acinetobacter species on immune responses in vitro and in vivo. Methods: The skin microbiota of the study subjects was identified by using 16S rRNA sequencing. PBMCs were analyzed for baseline and allergen-stimulated mRNA expression. In in vitro assays human monocyte-derived dendritic cells and primary keratinocytes were incubated with Acinetobacter lwoffii. Finally, in in vivo experiments mice were injected intradermally with A lwoffii during the sensitization phase of the asthma protocol, followed by readout of inflammatory parameters.

Research paper thumbnail of Räsänen, L., Lehto, M., Jokinen, I. & Leinikki, P. Polyclonal antibody formation of human lymphocytes to bacterial components. Immunology 58, 577-581

Immunology

The capacity of various bacterial components to induce antibody formation in human lymphocyte cul... more The capacity of various bacterial components to induce antibody formation in human lymphocyte cultures was studied in the present investigation. Antibody levels were determined by an enzyme-linked immunosorbent assay (ELISA). Lipopolysaccharide (LPS), bacterial cell walls (CW, isolated from Bacillus subtilis and Staphylococcus aureus Wood 46) and peptidoglycans (PG) appeared to stimulate IgM, IgG and IgA secretion, whereas lysozyme-solubilized PG and teichoic acids (TA) were ineffective. Also, umbilical cord blood lymphocytes produced IgM after stimulation with LPS, CW and PG. Coculture experiments with purified lymphocytes and monocytes indicated that B-cell differentiation was dependent on both T cells and monocytes, and that T-cell derived factors could derived factors could partially substitute for T cells.

Research paper thumbnail of Polyclonal response of human lymphocytes to Chlamydia trachomatis

Infection and Immunity

The mitogenicity of Chlamydia trachomatis was investigated. Umbilical cord blood cells from healt... more The mitogenicity of Chlamydia trachomatis was investigated. Umbilical cord blood cells from healthy newborns were used. These cells were stimulated in cultures with partially purified C. trachomatis elementary bodies. Proliferation of cultured lymphocytes and secreted immunoglobulins and leukocyte migration inhibitory factor were measured in the culture supernatants. Our results showed that C. trachomatis is able to elicit polyclonal antibody, lymphokine, and DNA synthesis.

Research paper thumbnail of Concentrations of tumor-associated trypsin inhibitor and C-reactive protein in serum in acute pelvic inflammatory disease

Clinical Chemistry

We measured tumor-associated trypsin inhibitor (TATI) and C-reactive protein (CRP) in serum of 29... more We measured tumor-associated trypsin inhibitor (TATI) and C-reactive protein (CRP) in serum of 29 patients with proven pelvic inflammatory disease (PID). TATI values were increased in seven (24%), paralleling increases in CRP. TATI was increased by about 3.5-fold in seven of eight patients with CRP concentrations greater than 90 mg/L, but in none of 21 patients with CRP concentrations less than 90 mg/L. TATI concentration and severity of PID as determined by laparoscopy or endometrial biopsy were not correlated. These results suggest that, in severe infections, regulation of TATI synthesis resembles that of acute-phase proteins.

Research paper thumbnail of Enrichment of dendritic cells from human peripheral blood

Journal of Leukocyte Biology

A simplified method is described for purification of dendritic cells from human peripheral blood.... more A simplified method is described for purification of dendritic cells from human peripheral blood. The method is based on depletion of phagocytes with carbonyl iron and magnet, followed by centrifugation of nonphagocytic cells on Percoll and elimination of contaminating T lymphocytes, B lymphocytes, natural killer cells, and monocytes from the low-density cell fraction by treatment with monoclonal antibodies and complement. The purity of enriched dendritic cells was about 80% and these cells represented 0.2% of the starting mononuclear cell population. Dendritic cells were potent autologous and allogeneic stimulators in mixed leukocyte cultures.

Research paper thumbnail of Negligible respiratory irritation and inflammation potency of pigmentary TiO 2 in mice

Inhalation Toxicology, 2015

Titanium dioxide (TiO2) is manufactured in millions of tons yearly, and it is used widely as pigm... more Titanium dioxide (TiO2) is manufactured in millions of tons yearly, and it is used widely as pigment in various applications. Until recently, TiO2 was considered toxicologically harmless and without adverse health effects. In this study, respiratory irritation and inflammation potencies of commercially available pigmentary TiO2 particles (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5 µm, rutile) were studied. Single head-only exposures (30 min) of male Crl:OF1 mice at mass concentrations 6, 11, 21, and 37 mg/m(3), and repeated exposures (altogether 16 h, 1 h/day, 4 days/week for 4 weeks) of female BALB/c/Sca mice at mass concentration of 16 mg/m(3) to pigmentary TiO2 were conducted. Minor sensory irritation was observed during acute and repeated exposures seen as elongation of the break after the inhalation, which is typical in sensory irritation, and caused by closure of the glottis inhibiting airflow from the lungs after inspiration. No pulmonary irritation, airflow limitation, nasal or pulmonary inflammation was observed. In conclusion, the respiratory irritation and inflammation potencies of the studied pigmentary TiO2 particles seemed to be low and thus can serve as an ideal control exposure agent in short-term studies in mice.

Research paper thumbnail of Topically applied ZnO nanoparticles suppress allergen induced skin inflammation but induce vigorous IgE production in the atopic dermatitis mouse model

Particle and Fibre Toxicology

Background Metal oxide nanoparticles such as ZnO are used in sunscreens as they improve their opt... more Background Metal oxide nanoparticles such as ZnO are used in sunscreens as they improve their optical properties against the UV-light that causes dermal damage and skin cancer. However, the hazardous properties of the particles used as UV-filters in the sunscreens and applied to the skin have remained uncharacterized.Methods Here we investigated whether different sized ZnO particles would be able to penetrate injured skin and injured allergic skin in the mouse atopic dermatitis model after repeated topical application of ZnO particles. Nano-sized ZnO (nZnO) and bulk-sized ZnO (bZnO) were applied to mechanically damaged mouse skin with or without allergen/superantigen sensitization. Allergen/superantigen sensitization evokes local inflammation and allergy in the skin and is used as a disease model of atopic dermatitis (AD).ResultsOur results demonstrate that only nZnO is able to reach into the deep layers of the allergic skin whereas bZnO stays in the upper layers of both damaged and...

Research paper thumbnail of Invariant Natural Killer T Cells Play a Role in Chemotaxis, Complement Activation and Mucus Production in a Mouse Model of Airway Hyperreactivity and Inflammation

PLOS ONE, 2015

CD1d-restricted invariant natural killer T (iNKT) cells play a critical role in the induction of ... more CD1d-restricted invariant natural killer T (iNKT) cells play a critical role in the induction of airway hyperreactivity (AHR). After intranasal alpha-galactosylceramide (α-GalCer) administration, bronchoalveolar lavage fluid (BALF) proteins from mouse lung were resolved by two-dimensional differential gel electrophoresis (2D-DIGE), and identified by tandem mass spectroscopy. A lack of iNKT cells prevented the development of airway responses including AHR, neutrophilia and the production of the proinflammatory cytokines in lungs. Differentially abundant proteins in the BALF proteome of α-GalCer-treated wild type mice included lungkine (CXCL15), pulmonary surfactant-associated protein D (SFTPD), calciumactivated chloride channel regulator 1 (CLCA1), fragments of complement 3, chitinase 3like proteins 1 (CH3LI) and 3 (CH3L3) and neutrophil gelatinase-associated lipocalin (NGAL). These proteins may contribute to iNKT regulated AHR via several mechanisms: altering leukocyte chemotaxis, increasing airway mucus production and possibly via complement activation.

Research paper thumbnail of A single aspiration of rod-like carbon nanotubes induces asbestos-like pulmonary inflammation mediated in part by the IL-1R

Toxicological Sciences, 2015

Carbon nanotubes (CNT) have been eagerly studied because of their multiple applications in produc... more Carbon nanotubes (CNT) have been eagerly studied because of their multiple applications in product development, and potential risks on health. We investigated the difference of two different CNT and asbestos in inducing pro-inflammatory reactions in C57BL/6 mice after single pharyngeal aspiration exposure. We used long tangled, and long rod-like CNT as well as crocidolite asbestos at a dose of 10 or 40 µg/mouse. The mice were sacrificed 4 and 16 hours or 7, 14 and 28 days after the exposure. To find out the importance of a major inflammatory marker IL-1β in CNT induced pulmonary inflammation, we used etanercept and anakinra as antagonists as well as IL1R-/- mice. The results showed that rod-like CNT, and asbestos in lesser extent, induced strong pulmonary neutrophilia accompanied by the pro-inflammatory cytokines and chemokines 16 h after the exposure. Seven days after the exposure neutrophilia had essentially disappeared but strong pulmonary eosinophilia peaked in rod-like CNT and asbestos exposed groups. After 28 days, pulmonary granulomas, goblet cell hyperplasia and Charcot-Leyden-like crystals containing acidophilic macrophages were observed especially in rod-like CNT exposed mice. IL-1R-/- mice and antagonists treated mice exhibited a significant decrease in neutrophilia and mRNA levels of pro-inflammatory cytokines at 16 h. However, rod-like CNT induced Th2 type inflammation evidenced by the expression of IL-13 and mucus production, was unaffected in IL-1R-/- mice at 28 days. This study provides knowledge about the pulmonary effects induced by a single exposure to the CNT and contributes to hazard assessment of carbon nanomaterials upon airway exposure.

Research paper thumbnail of Co-exposure with fullerene may strengthen health effects of organic industrial chemicals

PloS one, 2014

In vitro toxicological studies together with atomistic molecular dynamics simulations show that o... more In vitro toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C60 fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, m-cresol, and toluene which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolized in workplace air. Unfiltered and filtered mixtures of C60 and organic chemicals represent different co-exposure scenarios in in vitro studies where acute cytotoxicity and immunotoxicity of C60 and organic chemicals are tested together and alone by using human THP-1-derived macrophages. Statistically significant co-effects are observed for an unfiltered mixture of benzaldehyde and C60 that is more cytotoxic than benzaldehyde alone, and for a filtered mixture of m-cresol and C60 that is sligh...

Research paper thumbnail of Immediate and delayed hypersensitivity reactions to birch pollen in patients with atopic dermatitis

Acta dermato-venereologica, 1992

We investigated immediate and delayed hypersensitivity to birch pollen in 10 patients with atopic... more We investigated immediate and delayed hypersensitivity to birch pollen in 10 patients with atopic dermatitis (AD) who had experienced a worsening of their eczema during the birch pollen season. The patients were prick- and patch-tested and antigen-induced basophil histamine release and lymphocyte proliferation were measured. 9/10 birch pollen-allergic patients proved positive in the histamine release test and the results correlated with specific IgE levels measured by RAST. Birch pollen antigen induced lymphocyte proliferation in 6/10 patients, but a positive patch test result was obtained in only one case. Both peripheral blood monocytes and purified epidermal Langerhans' cells were able to present birch pollen antigen to T cells, although Langerhans' s cells seemed to function less efficiently in this respect.

Research paper thumbnail of Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans

Epidemiological studies have shown that short or insufficient sleep is associated with increased ... more Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complemented with pathway and transcription factor analysis. Expression levels of the ten most up-regulated and ten most down-regulated transcripts were correlated with subjective assessment of insufficient sleep in a population cohort (N = 472). Experimental sleep restriction altered the expression of 117 genes. Eight of the 25 most up-regulated transcripts were related to immune function. Accordingly, fifteen of the 25 most up-regulated Gene Ontology pathways were also related to immune function, including those for B cell activation, interleukin 8 production, and NF-κB signaling (P<0.005). Of the ten most up-regulated genes, expression of STX16 correlated negatively with self-reported insufficient sleep in a population sample, while three other genes showed tendency for positive correlation. Of the ten most down-regulated genes, TBX21 and LGR6 correlated negatively and TGFBR3 positively with insufficient sleep. Partial sleep restriction affects the regulation of signaling pathways related to the immune system. Some of these changes appear to be long-lasting and may at least partly explain how prolonged sleep restriction can contribute to inflammation-associated pathological states, such as cardiometabolic diseases.

Research paper thumbnail of Changed numbers of circulating immune cells after cumulative partial sleep deprivation and subsequent recovery sleep

Research paper thumbnail of CELL-MEDIATED AND HUMORAL IMMUNITY TO MUMPS VIRUS ANTIGEN

Acta Pathologica Microbiologica Scandinavica Series C: Immunology, 1986

Cell-mediated and humoral immunity to mumps virus antigen. Acta path. microbiol. immunol. scand. ... more Cell-mediated and humoral immunity to mumps virus antigen. Acta path. microbiol. immunol. scand. Sect. C. 94: 201-206, 1986. In the present study, cell-mediated and humoral immunity to mumps virus was investigated. The study population consisted of 25 subjects of whom 17 were initially seropositive for mumps. Serum antibody levels and lymphocyte blast transformation activity were measured before and after vaccination with inactivated vaccine. In addition, the subjects were skin tested and HLA-typed. Significant antibody responses, measured by enzyme-linked immunosorbent assay (ELSA), were observed after vaccination in all immunoglobulin classes. However, the elevation in antibody levels was usually transient in both seronegative and seropositive subjects. The IgA response was significantly higher in the seropositive than in the seronegative group, but no such difference was found in IgM or IgG antibodies. Vaccination also caused a significant but transient rise in lymphocyte blast transformation activity. Transformation results parallelled skin-test results and seropositivity, but not antibody levels, in the seropositive group. Pronounced IgA reactivity was significantly associated with Dw3 and Dw4 (DR3 and DR4) antigens. No HLA association was observed in IgG or IgM levels or in transformation activity.

Research paper thumbnail of SUPPRESSION OF AUTOLOGOUS MIXED LEUKOCYTE REACTION IN TYPE-1 DIABETES-MELLITUS BY INVIVO-ACTIVATED T LYMPHOCYTES

Clinical Immunology and Immunopathology, 1989

Research paper thumbnail of Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation

The Journal of allergy and clinical immunology, 2014

The human commensal microbiota interacts in a complex manner with the immune system, and the outc... more The human commensal microbiota interacts in a complex manner with the immune system, and the outcome of these interactions might depend on the immune status of the subject. Previous studies have suggested a strong allergy-protective effect for Gammaproteobacteria. Here we analyze the skin microbiota, allergic sensitization (atopy), and immune function in a cohort of adolescents, as well as the influence of Acinetobacter species on immune responses in vitro and in vivo. The skin microbiota of the study subjects was identified by using 16S rRNA sequencing. PBMCs were analyzed for baseline and allergen-stimulated mRNA expression. In in vitro assays human monocyte-derived dendritic cells and primary keratinocytes were incubated with Acinetobacter lwoffii. Finally, in in vivo experiments mice were injected intradermally with A lwoffii during the sensitization phase of the asthma protocol, followed by readout of inflammatory parameters. In healthy subjects, but not in atopic ones, the rel...