Surfactant protein D and asthma (original) (raw)
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American Journal of Respiratory and Critical Care Medicine, 2011
Rationale: Surfactant protein D (SP-D), a 43-kD collectin, is synthesized and secreted by airway epithelia as a dodecamer formed by assembly of four trimeric subunits. We have previously shown that the quaternary structure of SP-D can be altered during inflammatory lung injury through its modification by S-nitrosylation, which in turn alters its functional behavior producing a proinflammatory response in effector cells. Objectives: We hypothesized that alterations in structure and function of SP-D may occur in humans with acute allergic inflammation. Methods: Bronchoalveolar lavage (BAL) fluid was collected from 15 nonsmoking patients with mild intermittent allergic asthma before and 24 hours after segmental provocation with saline, allergen, LPS, and mixtures of allergen and LPS. Structural modifications of SP-D were analyzed by native and sodium dodecyl sulfate gel electrophoresis. Measurements and Main Results: The multimeric structure of native SP-D was found to be disrupted after provocation with allergen or a mixture of allergen and LPS. Interestingly, under reducing conditions, sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that 7 of 15 patients with asthma developed an abnormal cross-linked SP-D band after segmental challenge with either allergen or a mixture of allergen with LPS but not LPS alone. Importantly, patients with asthma with cross-linked SP-D demonstrated significantly higher levels of BAL eosinophils, nitrogen oxides, IL-4, IL-5, IL-13, and S-nitrosothiol-SP-D compared with patients without cross-linked SP-D. Conclusions: We conclude that segmental allergen challenge results in changes of SP-D multimeric structure and that these modifications are associated with an altered local inflammatory response in the distal airways.
Bronchial Asthma and Salivary Surfactant Protein D: Review Article
The Egyptian Journal of Hospital Medicine, 2021
Background: Chronic bronchial inflammation underlies asthma, which is a complex disease with varied and largely reversible blockage of the respiratory route. Asthma is a major public health issue that affects people of all ages around the world. Many countries are seeing an increase in the prevalence of this disease, particularly among children. Among children, asthma is the most frequent long-term condition, accounting for more than half of all missed school days, emergency room consultations, and hospitalizations. Surfactant Protein D, a pattern-recognition molecule, dampens elevated levels of particular antibodies, alveolar macrophage accumulation, eosinophilia, and subepithelial fibrosis and mucous metaplasia, as well as airway hyper-reactivity in allergic asthma in vivo. Objective: In order to discover the connection between children's bronchial asthma and surfactant protein D. Conclusion: Salivary SP-D is a simple, low-cost, quick, and noninvasive way to collect saliva from children. Salivary SP-D levels may be linked to asthma exacerbation severity and peripheral airway resistance.
Journal of Biological Chemistry, 2002
The N-terminal domains of the lung collectins, surfactant proteins A (SP-A) and D (SP-D), are critical for surfactant phospholipid interactions and surfactant homeostasis, respectively. To further assess the importance of lung collectin N-terminal domains in surfactant structure and function, a chimeric SP-D/SP-A (D/A) gene was constructed by substituting nucleotides encoding amino acids Asn 1 -Ala 7 of rat SP-A with the corresponding N-terminal sequences from rat SP-D, Ala 1 -Asn 25 .
Respiratory Research, 2012
Background: Allergen-containing subpollen particles (SPP) are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP)-D. The aim of the present study was to investigate the influence of SP-D in a complex three-dimensional human epithelial airway model, which simulates the most important barrier functions of the epithelial airway. The uptake of SPP as well as the secretion of pro-inflammatory cytokines was investigated. Methods: SPP were isolated from timothy grass and subsequently fluorescently labeled. A human epithelial airway model was built by using human Type II-pneumocyte like cells (A549 cells), human monocyte derived macrophages as well as human monocyte derived dendritic cells. The epithelial cell model was incubated with SPP in the presence and absence of surfactant protein D. Particle uptake was evaluated by confocal microscopy and advanced computer-controlled analysis. Finally, human primary CD4 + T-Cells were added to the epithelial airway model and soluble mediators were measured by enzyme linked immunosorbent assay or bead array. Results: SPP were taken up by epithelial cells, macrophages, and dendritic cells. This uptake coincided with secretion of pro-inflammatory cytokines and chemokines. SP-D modulated the uptake of SPP in a cell type specific way (e.g. increased number of macrophages and epithelial cells, which participated in allergen particle uptake) and led to a decreased secretion of pro-inflammatory cytokines. Conclusion: These results display a possible mechanism of how SP-D can modulate the inflammatory response to inhaled allergen.
Surfactant proteins SP-A and SP-D in human health and disease
Archivum immunologiae et therapiae experimentalis
Surfactant proteins A (SP-A) and D (SP-D) are lung surfactant-associated hydrophilic proteins that have been implicated in surfactant homeostasis and pulmonary innate immunity. They are collagen-containing C-type (calcium-dependent) lectins, called collectins, and are structurally similar to mannose-binding protein of the lectin pathway of the complement system. Being carbohydrate pattern-recognition molecules, they recognize a broad spectrum of pathogens and allergens via the lectin domain, with subsequent activation of immune cells via the collagen region, thus offering protection against infection and allergenic challenge. SP-A and SP-D have been shown to be involved in viral neutralization, clearance of bacteria, fungi, and apoptotic and necrotic cells, down-regulation of allergic reaction, and resolution of inflammation. Studies on single-nucleotide polymorphism, protein levels in broncho-alveolar lavage, and gene knock-out mice have clearly indicated an association between SP-...
Clinical & Experimental Allergy, 2001
Background Increasing evidence suggests that pulmonary surfactant protein A (SP-A) and D (SP-D) participate in the lung defence against pathogens. However, the role of surfactant proteins in the pathogenesis of allergen-induced airway inflammation has not been elucidated. In this study we examined the levels and distributions of SPA and SP-D in a dust mite (Dermatophagoides pteronyssinus, Der p) allergen-induced murine model of asthma. Methods The concentration of SPA and SP-D in the bronchoalveolar lavage fluid (BALF) and the distribution of surfactant proteins in the lung were assayed by ELISA and immunohistochemistry methods, respectively. The effect of surfactant proteins on allergen-induced pulmonary lymphocyte proliferation was also studied. Results We demonstrated that there were marked reductions of SPA and SP-D levels in the BALF of Der p-sensitized BALB/c mice at 48±72 h after allergen challenge (AC). Both purified SPA and SP-D were able to suppress, in a dose dependent manner, Der pstimulated intrapulmonary lymphocyte proliferation of naõ Ève mice with saline or allergen challenge, or of Der p-sensitized mice with saline challenge. On the contrary, this suppressive effect was mild (, 9%) on lymphocytes from sensitized mice after AC. Conclusion These results indicated the involvement of pulmonary surfactant proteins in the allergic bronchial inflammation of sensitized mice.
Surfactant Protein D in Respiratory and Non-Respiratory Diseases
Frontiers in Medicine
Surfactant protein D (SP-D) is a multimeric collectin that is involved in innate immune defense and expressed in pulmonary, as well as non-pulmonary, epithelia. SP-D exerts antimicrobial effects and dampens inflammation through direct microbial interactions and modulation of host cell responses via a series of cellular receptors. However, low protein concentrations, genetic variation, biochemical modification, and proteolytic breakdown can induce decomposition of multimeric SP-D into low-molecular weight forms, which may induce pro-inflammatory SP-D signaling. Multimeric SP-D can decompose into trimeric SP-D, and this process, and total SP-D levels, are partly determined by variation within the SP-D gene, SFTPD. SP-D has been implicated in the development of respiratory diseases including respiratory distress syndrome, bronchopulmonary dysplasia, allergic asthma, and chronic obstructive pulmonary disease. Disease-induced breakdown or modifications of SP-D facilitate its systemic leakage from the lung, and circulatory SP-D is a promising biomarker for lung injury. Moreover, studies in preclinical animal models have demonstrated that local pulmonary treatment with recombinant SP-D is beneficial in these diseases. In recent years, SP-D has been shown to exert antimicrobial and anti-inflammatory effects in various non-pulmonary organs and to have effects on lipid metabolism and pro-inflammatory effects in vessel walls, which enhance the risk of atherosclerosis. A common SFTPD polymorphism is associated with atherosclerosis and diabetes, and SP-D has been associated with metabolic disorders because of its effects in the endothelium and adipocytes and its obesity-dampening properties. This review summarizes and discusses the reported genetic associations of SP-D with disease and the clinical utility of circulating SP-D for respiratory disease prognosis. Moreover, basic research on the mechanistic links between SP-D and respiratory, cardiovascular, and metabolic diseases is summarized. Perspectives on the development of SP-D therapy are addressed.
Surfactant protein D alters allergic lung responses in mice and human subjects
Journal of Allergy and Clinical Immunology, 2008
Background: Surfactant protein (SP) D has been proposed to be protective in allergic airway responses. Objective: We aimed to determine the effect of SP-D deficiency on murine and human airway allergy. Methods: Immunologic responses of SP-D gene-deficient mice (Sftpd 2/2 ) at baseline and after 4 intranasal Aspergillus fumigatus exposures were assessed. In addition, the significance of a single nucleotide polymorphism (Met 11 Thr) in the human SP-D gene (known to decrease SP-D function) was investigated. Results: Macrophage and neutrophil bronchoalveolar lavage fluid levels and large airway mucus production were increased in naive Sftpd 2/2 mice in association with increased lung CCL17 levels and CD4 1 T cell numbers. T H 2-associated antibody levels (IgG1 and IgE) were significantly lower in 4-to 5-week-old Sftpd 2/2 mice (P < .05). Accordingly, naive Sftpd 2/2 splenocytes released significantly less IL-4 and IL-13 on anti-CD3/CD28 stimulation (P < .01). After intranasal allergen exposures, a modest decrease in bronchoalveolar lavage fluid eosinophilia and IL-13 levels was observed in Sftpd 2/2 mice compared with values seen in wild-type mice in association with decreased airway resistance (P < .01). A single nucleotide polymorphism in the SFTPD gene, affecting SP-D levels and pathogen binding, was associated with decreased atopy in black subjects and potentially lower asthma susceptibility in white subjects. Conclusion: Sftpd 2/2 mice have an impaired systemic T H 2 response at baseline and reduced inflammation and airway responses after allergen exposure. Translational studies revealed that a polymorphism in the SFTPD gene was associated with lower atopy and possibly asthma susceptibility. Taken together, these results support the hypothesis that SP-D-dependent innate immunity influences atopy and asthma. (J Allergy Clin Immunol 2008;121:1140-7.)
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2002
Background Structural remodelling of airways in asthma that follows inflammation may be affected by surfactant protein D (SP-D)-mediated effects on the immune response. Objective To determine potential sites of SP-D interaction with the pulmonary immune response, we examined the distribution of immunoreactive SP-D in an experimental model of allergen-induced airway inflammation using immunohistochemistry, biochemical methods and in situ hybridization. Methods The experimental model used subcutaneous injection of ovalbumin in adult rats, which induced an airway response to inhaled nebulized ovalbumin. Three groups of rats (ovalbumin, ovalbumin dexamethasone and saline) were challenged thrice weekly for 3 weeks. A fourth group of seven rats (naive) were taken from the same delivery of rats as the other groups. Lungs were then lavaged to determine total cell count, eosinophil count, ovalbumin-specific IgE by enzymelinked immunosorbent assay and SP-D by immunoblot. Tissue samples were fixed and embedded, and sections were studied for the infiltration of eosinophils and for expression of SP-D protein by histochemistry and mRNA by in situ hybridization. Results Ovalbumin induced perivascular and peribronchiolar eosinophilia which could be prevented by dexamethasone treatment. In addition, the ovalbumin-specific IgE levels in serum and bronchoalveolar lavage fluid of ovalbumin-challenged animals were enhanced. Increased amount of SP-D in lavage and tissue, particularly in type II pneumocytes, in Clara cells and, surprisingly, in hyperplastic goblet cells of inflamed lungs was found. SP-D mRNA was detected in goblet cells as well as in type II pneumocytes and Clara cells. Dexamethasone treatment did not affect level of SP-D immunoreactivity.