title: Surfactant protein A modulates cell surface expression of CR3 on alveolar macrophages and enhances CR3-mediated phagocytosis.
abstract: Pulmonary surfactant protein A (SP-A), a member of the collectin family, plays an important role in innate immune defense of the lung. In this study, we examined the role of SP-A in modulating complement receptor-mediated phagocytosis. Complement receptors (CR), CR3 (CD11b), and CR4 (CD11c) were expressed at reduced levels on the surface of alveolar macrophages from Sp-a(-/-) compared with Sp-a(+/+) mice. Administration of intratracheal SP-A to Sp-a(-/-) mice induced the translocation of CR3 from alveolar macrophage intracellular pools to the cell surface. Intratracheal challenge with Haemophilus influenza enhanced CR3 expression on the surface of alveolar macrophages from Sp-a(-/-) and Sp-a(+/+) mice, but relative expression remained lower in the Sp-a(-/-) mice at all time points post-inoculation. The effects of SP-A on macrophage and neutrophil CR3 redistribution between intracellular and cell surface pools were restricted to cells isolated from the lung. SP-A augmented CR3-mediated phagocytosis in a manner that was attenuated by N-glycanase or collagenase treatment of SP-A, implicating the N-linked sugar and collagen-like domains in that function. The binding of CR3 to SP-A was calcium dependent and mediated by the I-domain of CR3 and to a lesser extent by the CR3 lectin domain. Mapping of the domains of SP-A that were required for optimal binding to CR3 revealed that the N-linked sugars were more critical than the collagen-like domain or the extent of oligomeric assembly. We conclude that SP-A modulates the cell surface expression of CR3 on alveolar macrophages, binds to CR3, and enhances CR3-mediated phagocytosis.
authors.affiliation: Department of Pediatrics, Division of Critical Care Medicine, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Gil
authors.forename: Francis X
authors.initials: FX
authors.lastname: McCormack
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Levine
mesh_terms: D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation; D006192:Haemophilus Infections / Q000235:genetics / Q000378:metabolism*; D006193:Haemophilus influenzae; D016167:Integrin alphaXbeta2 / Q000235:genetics / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D010449:Peptide Mapping; D010587:Phagocytosis; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*
chemical_list: D016167:Integrin alphaXbeta2; D016177:Macrophage-1 Antigen; D037662:Pulmonary Surfactant-Associated Protein A; D002118:Calcium