E. Bissonnette - Academia.edu (original) (raw)

Papers by E. Bissonnette

Research paper thumbnail of Asbestos Fibers and Silica Particles Stimulate Rat Alveolar Macrophages To Release Tumor Necrosis Factor: Autoregulatory Role of Leukotriene B4

American Review of Respiratory Disease, 1989

Alveolar macrophages (AM) can play a crucial role in the pathogenesis of pulmonary disease via th... more Alveolar macrophages (AM) can play a crucial role in the pathogenesis of pulmonary disease via their ability to produce potent inflammatory and fibrogenic mediators. We found that rat AM cultured with 1 to 100 micrograms/ml of silica particles or asbestos fibers produced tumor necrosis factor (TNF) and leukotriene B4 (LTB4) in a concentration-dependent fashion, whereas latex beads, an inert phagocytic stimulus, failed to induce significant augmentation of either TNF or LTB4. In a time course study, AM stimulated for 2 h with silica or asbestos produced an increased amount of LTB4, which preceded the rise in TNF activity detected 7 and 24 h after culture initiation. The induction appears to involve the synthesis of new protein since actinomycin D and cycloheximide abrogate the majority of the stimulatory effect. We next examined the role of LTB4 in mineral-dust-induced TNF production. The lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA) and AA861 used at 1 to 50 micrograms/ml reduced in a concentration-dependent fashion asbestos- or silica-stimulated TNF release. On the other hand, "reconstitutive" experiments in which we added exogenous LTB4 (10(-14) to 10(-8) M) to AM treated with lipoxygenase inhibitors showed partial restoration of TNF production induced by chrysotile or silica, with peak effect at 10(-10)M LTB4. The present study demonstrated that AM incubated in the presence of chrysotile A or silica can produce both LTB4 and TNF and that endogenous lipoxygenase metabolites as well as exogenous LTB4 can act to amplify TNF production. These observations suggest a common mechanism by which asbestos and silica may modulate the production of inflammatory and fibrogenic cytokines.

Research paper thumbnail of Changes in lymphocyte function and lung histology during the development of asbestosis and silicosis in the mouse

Research communications in chemical pathology and pharmacology, 1989

In order to study changes in lung histology and lymphocyte function during the development of pne... more In order to study changes in lung histology and lymphocyte function during the development of pneumoconiosis, three groups of Balb/c mice were intratracheally instilled with either saline, chrysotile asbestos or silica particles and then sacrificed at different times. Asbestos-instilled mice showed collagen deposits at 2 months while silica-instilled mice showed severe fibrosis at that time. Stimulation of splenic cells with LPS was not affected by instillation of the toxic particles. Stimulation with PHA and ConA, however, induced increased responses especially at 3 and 6 months after instillation of asbestos or silica. A diminution of mitogen-induced proliferation was observed in aged mice. There was no correlation between changes in splenic cell proliferation and development of fibrosis. Asbestos fibers added in vitro, inhibited PHA and ConA-induced proliferation, partially due to prostaglandin (PG) production and to the presence of the fibers during the assay. When asbestos fibe...

Research paper thumbnail of Combined radiotherapy, chemotherapy, and maltose tetrapalmitate immunotherapy in the treatment of 4'dimethylaminoazobenzene-induced liver cancer

Anticancer research

Therapeutic effects of radiotherapy (R), chemotherapy, and maltose tetrapalmitate (MTP) immunothe... more Therapeutic effects of radiotherapy (R), chemotherapy, and maltose tetrapalmitate (MTP) immunotherapy alone and in combinations were tried against 4' dimethylaminoazobenzene (DAB) induced primary liver cancer in Wistar rats in three separate protocols. Rats were fed a low protein synthetic diet containing 0.06% DAB for 90-120 days. Around 90 days, liver cancers developed in all the animals. In the first protocol, animals were either left untreated or treated with cyclophosphamide (Cy), MTP (i.p. or oral) and Cy plus oral MTP. Rats in the MTP (i.p.) group maintained a steady liver weight but neither Cy nor Cy + MTP influenced the survival time or liver weight. In the second protocol, R as well as a 3-drug combination at 2 dose levels were tried alone and with MTP before or soon after cessation of DAB feeding. Survival times were decreased by R and chemotherapy due to combined toxicities of DAB and treatments and were partially restored by MTP. In the third protocol, MTP, R, and C...

Research paper thumbnail of Effect of maltose tetrapalmitate on tumor vascularization and tumor growth

Anticancer research

C3HBA mammary tumor (H-2k) was implanted s.c. by trocar in MTP responder C3H/HeN (H-2k) and non-r... more C3HBA mammary tumor (H-2k) was implanted s.c. by trocar in MTP responder C3H/HeN (H-2k) and non-responder C3H/HeJ (H-2k) female mice. One half of the animals received MTP i.p. The size of the tumor was measured everyday. Tumor growth was slightly slower in the C3H/HeJ than in the C3H/HeN. MTP treatment was effective only for the tumor implanted in the C3H/HeN. Microscopic and microscopic visualization of the tumor 1, 2, 3, and 15 days after tumor implantation and MTP treatment revealed poor vascular development in the MTP-treated C3H/HeN compared to untreated controls at days 2 and 3.

Research paper thumbnail of Platelet-activating factor (PAF) enhances tumor necrosis factor production by alveolar macrophages. Prevention by PAF receptor antagonists and lipoxygenase …

The Journal of …, 1989

... CLAIRE DUBOIS, ELYSE BISSONNETTE, AND MAREK ROLA-PLESZCZYNSKI' ... czynski. MD. Immunolo... more ... CLAIRE DUBOIS, ELYSE BISSONNETTE, AND MAREK ROLA-PLESZCZYNSKI' ... czynski. MD. Immunology Division, Faculty of Medicine, University of Correspondence and request for reprints address: Marek Rola-Plesz-Sherbrooke. ...

Research paper thumbnail of Mast Cell Response to Formaldehyde

International Archives of Allergy and Immunology, 1992

ABSTRACT

Research paper thumbnail of Inhibition of Alveolar Macrophage Cytotoxicity by Asbestos: Possible Role of Prostaglandins

Asbestosis and slllcosis are chronic, fibrosing lung diseases due to prolonged Inhalation of asbe... more Asbestosis and slllcosis are chronic, fibrosing lung diseases due to prolonged Inhalation of asbestos fibers or silica particles. However, little is known about the implication of these toxic dusts on cell-mediated cytotoxicity. Among the first types of cells that are in contact with the dusts are the alveolar macrophages (AM). We studied the effect of different concentrations of UICC chrysotile

Research paper thumbnail of A sphingosine-1-phosphate receptor 1 agonist inhibits tertiary lymphoid tissue reactivation and hypersensitivity in the lung

Mucosal Immunology

Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary l... more Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P 1) regulates key mechanisms underlying lymphoid tissue biology and its chemical modulation causes lymphocyte retention in lymph nodes. Given the putative immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated whether or not chemical modulation of S1P 1 caused lymphocyte retention within TLTs in a model of hypersensitivity pneumonitis. Mice were exposed subchronically to Methanosphaera stadtmanae (MSS) in order to induce an hypersensitivity pneumonitis-like disease. MSS exposure induced B-cell-rich TLTs surrounded by S1P 1-positive microvessels. Upon MSS rechallenge, the S1P 1 agonist RP001 prevented the pulmonary increase of CXCL13, a chief regulator of B-cell recruitment in lymphoid tissues. This was associated with a complete inhibition of MSS rechallenge-induced TLT enlargement and with a 2.3-fold reduction of MSS-specific antibody titers in the lung. Interference with TLT reactivation was associated with a 77% reduction of neutrophil accumulation and with full inhibition of protein-rich leakage in the airways. Thus, an S1P 1 agonist hinders TLT enlargement upon antigenic rechallenge and inhibits key pathognomonic features of experimental hypersensitivity pneumonitis.

Research paper thumbnail of PAF-acether enhances the production of tumor necrosis factor by human and rodent lymphocytes and macrophages

Research paper thumbnail of Leukotriene B4 and Tumor Necrosis Factor Production after in vitro Exposure of Rat Alveolar Macrophages to Mineral Dust: Potential Role in Fibrogenesis

Effects of Mineral Dusts on Cells, 1989

Research paper thumbnail of Modulation of Macrophage-Mediated Cytotoxicity by Toxic Particles

Effects of Mineral Dusts on Cells, 1989

Research paper thumbnail of IFN-gamma potentiates the release of TNF-alpha and MIP-1alpha by alveolar macrophages during allergic reactions

American journal of respiratory cell and molecular biology, 1999

Viral infections play an important role in the exacerbation of asthma. The production of interfer... more Viral infections play an important role in the exacerbation of asthma. The production of interferons (IFNs) is well known to limit viral spread, but IFN-gamma can also prime alveolar macrophages to release more inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-1alpha (MIP-1alpha). Given the importance of these cytokines, we have investigated the effect of IFN-gamma on their release by alveolar macrophages during stimulation by immunoglobulin (Ig)E/anti-IgE. Alveolar macrophages from normal or Nippostrongylus brasiliensis-infected rats, the latter having increased numbers of low-affinity receptors for IgE (Fcepsilon RII) on their alveolar macrophages, were treated with IgE for 2 h and stimulated with anti-IgE for 18 h. The increase of TNF-alpha release (153 +/- 48 pg/10(6) cells) by IgE/anti-IgE occurred only with alveolar macrophages from infected rats. The messenger RNA level for TNF-alpha in rat alveolar macrophages was als...

Research paper thumbnail of Mechanisms of macrophage stimulation through CD8: macrophage CD8alpha and CD8beta induce nitric oxide production and associated killing of the parasite Leishmania major

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1998

Prior studies demonstrated that rat macrophages express CD8, which differs from T lymphocyte CD8 ... more Prior studies demonstrated that rat macrophages express CD8, which differs from T lymphocyte CD8 within the ligand binding domain. We investigated whether stimulation of macrophage CD8 could induce mediator release and regulate host defense. Cross-linking either CD8alpha (OX8, 5 microg/ml) or CD8beta (341, 10 microg/ml) stimulated nitric oxide (NO) production, which correlated with an up-regulation of inducible NO synthase protein. Cell signaling inhibitors were used to elucidate the pathways of CD8alpha and CD8beta stimulation. Genistein (broad spectrum protein tyrosine kinase inhibitor, 10 microg/ml), PP1 (src family kinase inhibitor, 5 microg/ml), polymyxin B (protein kinase C (PKC) inhibitor, 100 microg/ml), and Ro 31-8220 (PKC inhibitor, 1 microM) significantly inhibited anti-CD8alpha- and anti-CD8beta-stimulated NO production and inducible NO synthase up-regulation, suggesting that tyrosine kinase(s) (src family) and PKC are involved in CD8 signaling. In addition, cross-linkin...

Research paper thumbnail of Mast cells in asthma

Canadian respiratory journal : journal of the Canadian Thoracic Society

Research paper thumbnail of Anti-inflammatory effect of beta 2-agonists: inhibition of TNF-alpha release from human mast cells

The Journal of allergy and clinical immunology, 1997

Beta 2-agonists inhibit the release of preformed mediators such as histamine and newly synthesize... more Beta 2-agonists inhibit the release of preformed mediators such as histamine and newly synthesized mediators such as prostaglandin D2 from mast cells. However, although mast cells have been identified as an important source of several cytokines including tumor necrosis factor-alpha (TNF-alpha), there is no information about their regulation by beta 2-agonists. Thus given the importance of TNF-alpha in inflammation and the widespread use of beta 2-agonists, we investigated the effect of long-acting (salmeterol) and short-acting (salbutamol) beta 2-agonists on the secretion of TNF-alpha from human skin mast cells. Treatment of mast cells with salmeterol or salbutamol (100 nmol/L) inhibited the IgE-dependent release of TNF-alpha (82% and 74%, respectively). Moreover, 2-hour treatment with salmeterol, isoproterenol, or salbutamol inhibited mast cell cytotoxicity against a TNF-alpha-sensitive cell line, WEHI-164, with an IC50 of 71, 50, and 29 nmol/L, respectively. Specificity for beta-a...

Research paper thumbnail of Cytokine and drug modulation of TNF alpha in mast cells

Advances in experimental medicine and biology, 1996

Research paper thumbnail of Inhibitory effects of sulfasalazine and its metabolites on histamine release and TNF-alpha production by mast cells

Journal of immunology (Baltimore, Md. : 1950), 1996

Sulfasalazine is an effective treatment in some inflammatory diseases that exhibit mast cell (MC)... more Sulfasalazine is an effective treatment in some inflammatory diseases that exhibit mast cell (MC) hyperplasia. However, its effect on MC has been incompletely studied. We have established that sulfasalazine inhibits the release of histamine and TNF-alpha from MC. Sulfasalazine and its metabolites, 5-aminosalicylic acid (5-ASA) and to a lesser extent sulfapyridine, inhibited Ag-stimulated histamine release from rat peritoneal MC in a concentration-dependent manner with a 50% inhibitory concentration of 6 x 10(6)M, 8 x 10(-6)M, and 3 x 10(-4)M, respectively. Similar results were observed with sulfapyridine and 5-ASA on Ag-stimulated histamine release of another population of MC, namely rat intestinal mucosal MC, but sulfasalazine was markedly less potent than its metabolites. Interestingly, sulfasalazine and sulfapyridine, but not 5-ASA, inhibited Ag-stimulated TNF-alpha released by MC. Similar results were observed with MC-mediated cytotoxic activity in which sulfasalazine and sulfap...

Research paper thumbnail of Prostaglandins inhibit inflammatory mediator release from rat mast cells

Gastroenterology, 1993

Mast cells have been implicated in the pathogenesis of gastric ulceration. It is possible that pr... more Mast cells have been implicated in the pathogenesis of gastric ulceration. It is possible that prostaglandins exert cytoprotective effects by inhibiting the release of proulcerogenic mediators from mast cells. The effects of three prostaglandins on the release of platelet-activating factor, tumor necrosis factor, and histamine from rat mast cells (peritoneal and intestinal mucosal) activated with calcium ionophore or antigen were assessed. Upon stimulation with either agonist, intestinal mucosal and peritoneal mast cells released significant quantities of platelet-activating factor. Preincubation for 5 minutes with misoprostol, prostaglandin (PG)E2, 16,16-dimethyl PGE2, ketotifen, or PF-5901 concentration-dependently reduced ionophore-stimulated platelet-activating factor release; significant effects were observed with picomolar to nanomolar concentrations of the prostaglandins and micromolar concentrations of the other compounds. Tumor necrosis factor release from peritoneal and mu...

Research paper thumbnail of Interferons differentially regulate histamine and TNF-alpha in rat intestinal mucosal mast cells

Immunology, 1995

Mast cell (MC) heterogeneity has been well characterized in the rat where it has been shown that ... more Mast cell (MC) heterogeneity has been well characterized in the rat where it has been shown that connective tissue MC, often represented by peritoneal MC (PMC), and the intestinal mucosal MC (IMMC) exhibit many differences in mediator content and responsiveness to secretagogues and anti-allergic drugs. Pretreatment (20 hr) of PMC with interferon (IFN)-alpha/beta or IFN-gamma, significantly reduced antigen-stimulated histamine release. By contrast, for IMMC, the same IFN treatment did not modify antigen-stimulated histamine secretion. Although IFN treatment differentially modulates histamine secretion from PMC and IMMC, pretreatment of both MC types with IFN-alpha/beta or IFN-gamma inhibited their tumour-necrosis factor-alpha (TNF-alpha)-dependent cytotoxicity. In 20 hr of culture, IMMC spontaneously released 98 pg/10(6) MC of TNF-alpha, whereas PMC released about threefold more TNF-alpha, 282 pg/10(6) MC. In addition, direct assessment of stored TNF-alpha established that IMMC store...

Research paper thumbnail of Histone H1(0) expression during developmental growth of rat liver

Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire, 1983

Histone H1(0) appears in rat liver nuclei around the time of birth; it increases to near-adult le... more Histone H1(0) appears in rat liver nuclei around the time of birth; it increases to near-adult levels by 30 days of age, in waves which correlate with distinct phases of liver developmental growth. H1 emerges as the liver terminates the bulk of its proliferative activity, but it accumulates mainly during the terminal cytodifferentiation phases leading to polyploidization. Premature interruption of liver DNA synthesis in neonatal rats, with cytosine arabinoside or dexamethasone, induces some accumulation of H1 in the liver. Our data suggest that DNA synthesis arrest conditions in part, but is not the main developmental event underlying H1 expression during differentiation of rat liver.

Research paper thumbnail of Asbestos Fibers and Silica Particles Stimulate Rat Alveolar Macrophages To Release Tumor Necrosis Factor: Autoregulatory Role of Leukotriene B4

American Review of Respiratory Disease, 1989

Alveolar macrophages (AM) can play a crucial role in the pathogenesis of pulmonary disease via th... more Alveolar macrophages (AM) can play a crucial role in the pathogenesis of pulmonary disease via their ability to produce potent inflammatory and fibrogenic mediators. We found that rat AM cultured with 1 to 100 micrograms/ml of silica particles or asbestos fibers produced tumor necrosis factor (TNF) and leukotriene B4 (LTB4) in a concentration-dependent fashion, whereas latex beads, an inert phagocytic stimulus, failed to induce significant augmentation of either TNF or LTB4. In a time course study, AM stimulated for 2 h with silica or asbestos produced an increased amount of LTB4, which preceded the rise in TNF activity detected 7 and 24 h after culture initiation. The induction appears to involve the synthesis of new protein since actinomycin D and cycloheximide abrogate the majority of the stimulatory effect. We next examined the role of LTB4 in mineral-dust-induced TNF production. The lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA) and AA861 used at 1 to 50 micrograms/ml reduced in a concentration-dependent fashion asbestos- or silica-stimulated TNF release. On the other hand, "reconstitutive" experiments in which we added exogenous LTB4 (10(-14) to 10(-8) M) to AM treated with lipoxygenase inhibitors showed partial restoration of TNF production induced by chrysotile or silica, with peak effect at 10(-10)M LTB4. The present study demonstrated that AM incubated in the presence of chrysotile A or silica can produce both LTB4 and TNF and that endogenous lipoxygenase metabolites as well as exogenous LTB4 can act to amplify TNF production. These observations suggest a common mechanism by which asbestos and silica may modulate the production of inflammatory and fibrogenic cytokines.

Research paper thumbnail of Changes in lymphocyte function and lung histology during the development of asbestosis and silicosis in the mouse

Research communications in chemical pathology and pharmacology, 1989

In order to study changes in lung histology and lymphocyte function during the development of pne... more In order to study changes in lung histology and lymphocyte function during the development of pneumoconiosis, three groups of Balb/c mice were intratracheally instilled with either saline, chrysotile asbestos or silica particles and then sacrificed at different times. Asbestos-instilled mice showed collagen deposits at 2 months while silica-instilled mice showed severe fibrosis at that time. Stimulation of splenic cells with LPS was not affected by instillation of the toxic particles. Stimulation with PHA and ConA, however, induced increased responses especially at 3 and 6 months after instillation of asbestos or silica. A diminution of mitogen-induced proliferation was observed in aged mice. There was no correlation between changes in splenic cell proliferation and development of fibrosis. Asbestos fibers added in vitro, inhibited PHA and ConA-induced proliferation, partially due to prostaglandin (PG) production and to the presence of the fibers during the assay. When asbestos fibe...

Research paper thumbnail of Combined radiotherapy, chemotherapy, and maltose tetrapalmitate immunotherapy in the treatment of 4'dimethylaminoazobenzene-induced liver cancer

Anticancer research

Therapeutic effects of radiotherapy (R), chemotherapy, and maltose tetrapalmitate (MTP) immunothe... more Therapeutic effects of radiotherapy (R), chemotherapy, and maltose tetrapalmitate (MTP) immunotherapy alone and in combinations were tried against 4' dimethylaminoazobenzene (DAB) induced primary liver cancer in Wistar rats in three separate protocols. Rats were fed a low protein synthetic diet containing 0.06% DAB for 90-120 days. Around 90 days, liver cancers developed in all the animals. In the first protocol, animals were either left untreated or treated with cyclophosphamide (Cy), MTP (i.p. or oral) and Cy plus oral MTP. Rats in the MTP (i.p.) group maintained a steady liver weight but neither Cy nor Cy + MTP influenced the survival time or liver weight. In the second protocol, R as well as a 3-drug combination at 2 dose levels were tried alone and with MTP before or soon after cessation of DAB feeding. Survival times were decreased by R and chemotherapy due to combined toxicities of DAB and treatments and were partially restored by MTP. In the third protocol, MTP, R, and C...

Research paper thumbnail of Effect of maltose tetrapalmitate on tumor vascularization and tumor growth

Anticancer research

C3HBA mammary tumor (H-2k) was implanted s.c. by trocar in MTP responder C3H/HeN (H-2k) and non-r... more C3HBA mammary tumor (H-2k) was implanted s.c. by trocar in MTP responder C3H/HeN (H-2k) and non-responder C3H/HeJ (H-2k) female mice. One half of the animals received MTP i.p. The size of the tumor was measured everyday. Tumor growth was slightly slower in the C3H/HeJ than in the C3H/HeN. MTP treatment was effective only for the tumor implanted in the C3H/HeN. Microscopic and microscopic visualization of the tumor 1, 2, 3, and 15 days after tumor implantation and MTP treatment revealed poor vascular development in the MTP-treated C3H/HeN compared to untreated controls at days 2 and 3.

Research paper thumbnail of Platelet-activating factor (PAF) enhances tumor necrosis factor production by alveolar macrophages. Prevention by PAF receptor antagonists and lipoxygenase …

The Journal of …, 1989

... CLAIRE DUBOIS, ELYSE BISSONNETTE, AND MAREK ROLA-PLESZCZYNSKI' ... czynski. MD. Immunolo... more ... CLAIRE DUBOIS, ELYSE BISSONNETTE, AND MAREK ROLA-PLESZCZYNSKI' ... czynski. MD. Immunology Division, Faculty of Medicine, University of Correspondence and request for reprints address: Marek Rola-Plesz-Sherbrooke. ...

Research paper thumbnail of Mast Cell Response to Formaldehyde

International Archives of Allergy and Immunology, 1992

ABSTRACT

Research paper thumbnail of Inhibition of Alveolar Macrophage Cytotoxicity by Asbestos: Possible Role of Prostaglandins

Asbestosis and slllcosis are chronic, fibrosing lung diseases due to prolonged Inhalation of asbe... more Asbestosis and slllcosis are chronic, fibrosing lung diseases due to prolonged Inhalation of asbestos fibers or silica particles. However, little is known about the implication of these toxic dusts on cell-mediated cytotoxicity. Among the first types of cells that are in contact with the dusts are the alveolar macrophages (AM). We studied the effect of different concentrations of UICC chrysotile

Research paper thumbnail of A sphingosine-1-phosphate receptor 1 agonist inhibits tertiary lymphoid tissue reactivation and hypersensitivity in the lung

Mucosal Immunology

Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary l... more Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P 1) regulates key mechanisms underlying lymphoid tissue biology and its chemical modulation causes lymphocyte retention in lymph nodes. Given the putative immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated whether or not chemical modulation of S1P 1 caused lymphocyte retention within TLTs in a model of hypersensitivity pneumonitis. Mice were exposed subchronically to Methanosphaera stadtmanae (MSS) in order to induce an hypersensitivity pneumonitis-like disease. MSS exposure induced B-cell-rich TLTs surrounded by S1P 1-positive microvessels. Upon MSS rechallenge, the S1P 1 agonist RP001 prevented the pulmonary increase of CXCL13, a chief regulator of B-cell recruitment in lymphoid tissues. This was associated with a complete inhibition of MSS rechallenge-induced TLT enlargement and with a 2.3-fold reduction of MSS-specific antibody titers in the lung. Interference with TLT reactivation was associated with a 77% reduction of neutrophil accumulation and with full inhibition of protein-rich leakage in the airways. Thus, an S1P 1 agonist hinders TLT enlargement upon antigenic rechallenge and inhibits key pathognomonic features of experimental hypersensitivity pneumonitis.

Research paper thumbnail of PAF-acether enhances the production of tumor necrosis factor by human and rodent lymphocytes and macrophages

Research paper thumbnail of Leukotriene B4 and Tumor Necrosis Factor Production after in vitro Exposure of Rat Alveolar Macrophages to Mineral Dust: Potential Role in Fibrogenesis

Effects of Mineral Dusts on Cells, 1989

Research paper thumbnail of Modulation of Macrophage-Mediated Cytotoxicity by Toxic Particles

Effects of Mineral Dusts on Cells, 1989

Research paper thumbnail of IFN-gamma potentiates the release of TNF-alpha and MIP-1alpha by alveolar macrophages during allergic reactions

American journal of respiratory cell and molecular biology, 1999

Viral infections play an important role in the exacerbation of asthma. The production of interfer... more Viral infections play an important role in the exacerbation of asthma. The production of interferons (IFNs) is well known to limit viral spread, but IFN-gamma can also prime alveolar macrophages to release more inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-1alpha (MIP-1alpha). Given the importance of these cytokines, we have investigated the effect of IFN-gamma on their release by alveolar macrophages during stimulation by immunoglobulin (Ig)E/anti-IgE. Alveolar macrophages from normal or Nippostrongylus brasiliensis-infected rats, the latter having increased numbers of low-affinity receptors for IgE (Fcepsilon RII) on their alveolar macrophages, were treated with IgE for 2 h and stimulated with anti-IgE for 18 h. The increase of TNF-alpha release (153 +/- 48 pg/10(6) cells) by IgE/anti-IgE occurred only with alveolar macrophages from infected rats. The messenger RNA level for TNF-alpha in rat alveolar macrophages was als...

Research paper thumbnail of Mechanisms of macrophage stimulation through CD8: macrophage CD8alpha and CD8beta induce nitric oxide production and associated killing of the parasite Leishmania major

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1998

Prior studies demonstrated that rat macrophages express CD8, which differs from T lymphocyte CD8 ... more Prior studies demonstrated that rat macrophages express CD8, which differs from T lymphocyte CD8 within the ligand binding domain. We investigated whether stimulation of macrophage CD8 could induce mediator release and regulate host defense. Cross-linking either CD8alpha (OX8, 5 microg/ml) or CD8beta (341, 10 microg/ml) stimulated nitric oxide (NO) production, which correlated with an up-regulation of inducible NO synthase protein. Cell signaling inhibitors were used to elucidate the pathways of CD8alpha and CD8beta stimulation. Genistein (broad spectrum protein tyrosine kinase inhibitor, 10 microg/ml), PP1 (src family kinase inhibitor, 5 microg/ml), polymyxin B (protein kinase C (PKC) inhibitor, 100 microg/ml), and Ro 31-8220 (PKC inhibitor, 1 microM) significantly inhibited anti-CD8alpha- and anti-CD8beta-stimulated NO production and inducible NO synthase up-regulation, suggesting that tyrosine kinase(s) (src family) and PKC are involved in CD8 signaling. In addition, cross-linkin...

Research paper thumbnail of Mast cells in asthma

Canadian respiratory journal : journal of the Canadian Thoracic Society

Research paper thumbnail of Anti-inflammatory effect of beta 2-agonists: inhibition of TNF-alpha release from human mast cells

The Journal of allergy and clinical immunology, 1997

Beta 2-agonists inhibit the release of preformed mediators such as histamine and newly synthesize... more Beta 2-agonists inhibit the release of preformed mediators such as histamine and newly synthesized mediators such as prostaglandin D2 from mast cells. However, although mast cells have been identified as an important source of several cytokines including tumor necrosis factor-alpha (TNF-alpha), there is no information about their regulation by beta 2-agonists. Thus given the importance of TNF-alpha in inflammation and the widespread use of beta 2-agonists, we investigated the effect of long-acting (salmeterol) and short-acting (salbutamol) beta 2-agonists on the secretion of TNF-alpha from human skin mast cells. Treatment of mast cells with salmeterol or salbutamol (100 nmol/L) inhibited the IgE-dependent release of TNF-alpha (82% and 74%, respectively). Moreover, 2-hour treatment with salmeterol, isoproterenol, or salbutamol inhibited mast cell cytotoxicity against a TNF-alpha-sensitive cell line, WEHI-164, with an IC50 of 71, 50, and 29 nmol/L, respectively. Specificity for beta-a...

Research paper thumbnail of Cytokine and drug modulation of TNF alpha in mast cells

Advances in experimental medicine and biology, 1996

Research paper thumbnail of Inhibitory effects of sulfasalazine and its metabolites on histamine release and TNF-alpha production by mast cells

Journal of immunology (Baltimore, Md. : 1950), 1996

Sulfasalazine is an effective treatment in some inflammatory diseases that exhibit mast cell (MC)... more Sulfasalazine is an effective treatment in some inflammatory diseases that exhibit mast cell (MC) hyperplasia. However, its effect on MC has been incompletely studied. We have established that sulfasalazine inhibits the release of histamine and TNF-alpha from MC. Sulfasalazine and its metabolites, 5-aminosalicylic acid (5-ASA) and to a lesser extent sulfapyridine, inhibited Ag-stimulated histamine release from rat peritoneal MC in a concentration-dependent manner with a 50% inhibitory concentration of 6 x 10(6)M, 8 x 10(-6)M, and 3 x 10(-4)M, respectively. Similar results were observed with sulfapyridine and 5-ASA on Ag-stimulated histamine release of another population of MC, namely rat intestinal mucosal MC, but sulfasalazine was markedly less potent than its metabolites. Interestingly, sulfasalazine and sulfapyridine, but not 5-ASA, inhibited Ag-stimulated TNF-alpha released by MC. Similar results were observed with MC-mediated cytotoxic activity in which sulfasalazine and sulfap...

Research paper thumbnail of Prostaglandins inhibit inflammatory mediator release from rat mast cells

Gastroenterology, 1993

Mast cells have been implicated in the pathogenesis of gastric ulceration. It is possible that pr... more Mast cells have been implicated in the pathogenesis of gastric ulceration. It is possible that prostaglandins exert cytoprotective effects by inhibiting the release of proulcerogenic mediators from mast cells. The effects of three prostaglandins on the release of platelet-activating factor, tumor necrosis factor, and histamine from rat mast cells (peritoneal and intestinal mucosal) activated with calcium ionophore or antigen were assessed. Upon stimulation with either agonist, intestinal mucosal and peritoneal mast cells released significant quantities of platelet-activating factor. Preincubation for 5 minutes with misoprostol, prostaglandin (PG)E2, 16,16-dimethyl PGE2, ketotifen, or PF-5901 concentration-dependently reduced ionophore-stimulated platelet-activating factor release; significant effects were observed with picomolar to nanomolar concentrations of the prostaglandins and micromolar concentrations of the other compounds. Tumor necrosis factor release from peritoneal and mu...

Research paper thumbnail of Interferons differentially regulate histamine and TNF-alpha in rat intestinal mucosal mast cells

Immunology, 1995

Mast cell (MC) heterogeneity has been well characterized in the rat where it has been shown that ... more Mast cell (MC) heterogeneity has been well characterized in the rat where it has been shown that connective tissue MC, often represented by peritoneal MC (PMC), and the intestinal mucosal MC (IMMC) exhibit many differences in mediator content and responsiveness to secretagogues and anti-allergic drugs. Pretreatment (20 hr) of PMC with interferon (IFN)-alpha/beta or IFN-gamma, significantly reduced antigen-stimulated histamine release. By contrast, for IMMC, the same IFN treatment did not modify antigen-stimulated histamine secretion. Although IFN treatment differentially modulates histamine secretion from PMC and IMMC, pretreatment of both MC types with IFN-alpha/beta or IFN-gamma inhibited their tumour-necrosis factor-alpha (TNF-alpha)-dependent cytotoxicity. In 20 hr of culture, IMMC spontaneously released 98 pg/10(6) MC of TNF-alpha, whereas PMC released about threefold more TNF-alpha, 282 pg/10(6) MC. In addition, direct assessment of stored TNF-alpha established that IMMC store...

Research paper thumbnail of Histone H1(0) expression during developmental growth of rat liver

Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire, 1983

Histone H1(0) appears in rat liver nuclei around the time of birth; it increases to near-adult le... more Histone H1(0) appears in rat liver nuclei around the time of birth; it increases to near-adult levels by 30 days of age, in waves which correlate with distinct phases of liver developmental growth. H1 emerges as the liver terminates the bulk of its proliferative activity, but it accumulates mainly during the terminal cytodifferentiation phases leading to polyploidization. Premature interruption of liver DNA synthesis in neonatal rats, with cytosine arabinoside or dexamethasone, induces some accumulation of H1 in the liver. Our data suggest that DNA synthesis arrest conditions in part, but is not the main developmental event underlying H1 expression during differentiation of rat liver.