Non-Pulmonary Immune Functions of Surfactant Proteins A and D (original) (raw)
Related papers
Frontiers in Immunology, 2012
A and SP-D are hydrophilic, collagen-containing calcium-dependent lectins, which appear to have a range of innate immune functions at pulmonary as well as extrapulmonary sites. These proteins bind to target ligands on pathogens, allergens, and apoptotic cells, via C-terminal homotrimeric carbohydrate recognition domains, while the collagen region brings about the effector functions via its interaction with cell surface receptors. SPA and SP-D deal with various pathogens, using a range of innate immune mechanisms such as agglutination/aggregation, enhancement of phagocytosis, and killing mechanisms by phagocytic cells and direct growth inhibition. SPA and SP-D have also been shown to be involved in the control of pulmonary inflammation including allergy and asthma. Emerging evidence suggest that SPA and SP-D are capable of linking innate immunity with adaptive immunity that includes modulation of dendritic cell function and helper T cell polarization.This review enumerates immunological properties of SPA and SP-D inside and outside lungs and discusses their importance in human health and disease.
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-...
American Journal of Respiratory Cell and Molecular Biology, 2004
Surfactant protein (SP)-D, a 43-kD multifunctional collagen-like lectin, is synthesized and secreted by the airway epithelium. SP-D knockout (SP-D [Ϫ/Ϫ]) mice exhibit an increase in the number and size of airway macrophages, peribronchiolar inflammation, increases in metalloproteinase activity, and development of emphysema. Nitric oxide (NO) is involved in a variety of signaling processes, and because altered NO metabolism has been observed in inflammation, we hypothesized that alterations in its metabolism would underlie the proinflammatory state observed in SP-D deficiency. Examination of the bronchial alveolar lavage (BAL) from SP-D (Ϫ/Ϫ) mice reveals a significant increase in protein and phospholipid content and total cell count. NO production and inducible NO synthase expression were increased in the BAL; however, there was a decline in S-nitrosothiol (SNO) content in the BAL and a loss of SNO immunoreactivity within the tissue. This decline in SNO was accompanied by an increase in nitrotyrosine staining. We conclude that inflammation that occurs in SP-D deficiency results in an increase in NO production and a shift in the chemistry and targets of NO. We speculate that the proinflammatory response due to SP-D deficiency results, in part, from a disruption of NO-mediated signaling within the innate immune system. Surfactant protein (SP)-D is a member of a novel growing family of collagen-like lectins ("collectins") that are believed to play a role in non-antibody-mediated innate immune responses (1). SP-D shares considerable structural homology with other proteins of this type, including SPA , conglutinin, bovine collectin-43, and mannose-binding protein. SPA and SP-D are both multimeric Ca 2ϩ-binding lectins produced primarily by alveolar type II cells and nonciliated bronchiolar cells in the lung (2). In contrast to SPA , SP-D does not interact with major surfactant phospholipids and is not associated with lamellar bodies or tubular myelin. The primary function of these proteins appears to be in the modulation of host defense and inflammation, although the mechanism of their action has not been fully defined.
Surfactant protein D deficiency influences allergic immune responses
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2004
Background The collectin surfactant protein D (SP-D) confers protection against pulmonary infection and inflammation. Recent data suggest a role for SP-D in the modulation of allergic inflammation.
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.)
Journal of immunology (Baltimore, Md. : 1950), 1998
Components of the airspace-lining material may contribute to the local regulation of immune function within the lung. We report here that recombinant rat pulmonary surfactant-associated protein D (SP-D) inhibits the lectin- and anti-CD3-stimulated proliferation of human PBMCs. Inhibition was associated with a decreased production of IL-2, and the addition of human rIL-2 blocked the inhibitory action of SP-D. These effects were not inhibited by maltose, indicating that the inhibitory activity was not dependent upon the lectin activity of SP-D. Studies employing mutant SP-D lacking N-linked sugars or defective in multimerization further indicated that inhibition was not dependent upon cellular interactions with the N-linked oligosaccharide on SP-D or the oligomerization of trimeric SP-D subunits. Although a peptide containing an inverted DGR showed similar IL-2-dependent effects on anti-CD3-stimulated proliferation, deletion of the conserved DGRDGR sequence near the amino-terminal end...
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.
Expert Review of Proteomics, 2014
Surfactant protein D (SP-D), a C-type lectin, is known to protect against lung infection, allergy and inflammation. Its recombinant truncated form comprising homotrimeric neck and CRD region (rhSP-D) has been shown to bring down specific IgE levels, eosinophilia and restore Th2-Th1 homeostasis in murine models of lung hypersensitivity. SP-D knockout mice show intrinsic hypereosinophilia and airway hyper-responsiveness that can be alleviated by rhSP-D. The rhSP-D can bind activated eosinophils, inhibit chemotaxis and degranulation, and selectively induce oxidative burst and apoptosis in sensitized eosinophils. A global proteomics study of rhSP-D-treated eosinophilic cell line AML14.3D10 identified large-scale molecular changes associated with oxidative burst, cell stress and survival-related proteins potentially responsible for apoptosis induction. The data also suggested an involvement of RNA bindingand RNA splicing-related proteins. Thus, the proteomics approach yielded a catalog of differentially expressed proteins that may be protein signatures defining mechanisms of SP-Dmediated maintenance of homeostasis during allergy.