title: Surfactant protein A enhances alveolar macrophage phagocytosis of apoptotic neutrophils.
abstract: Surfactant protein A (SP-A) is an innate immune molecule that binds foreign organisms that invade the lungs and targets them for phagocytic clearance by the resident pulmonary phagocyte, the alveolar macrophage (AM). We hypothesized that SP-A binds to and enhances macrophage uptake of other nonself particles, specifically apoptotic polymorphonuclear neutrophils (PMNs). PMNs are recruited into the lungs during inflammation, but as inflammation is resolved, PMNs undergo apoptosis and are phagocytosed by AMs. We determined that SP-A increases AM phagocytosis of apoptotic PMNs 280 +/- 62% above the no protein control value. The increase is dose dependent, and heat-treated SP-A still enhanced uptake, whereas deglycosylated SP-A had significantly diminished ability to enhance phagocytosis. Surfactant protein D also increased phagocytosis of apoptotic PMNs by approximately 125%. However, other proteins that are structurally homologous to SP-A, mannose-binding lectin and complement protein 1q, did not. SP-A enhances phagocytosis via an opsonization-dependent mechanism and binds apoptotic PMNs approximately 4-fold more than viable PMNs. Also, binding of SP-A to apoptotic PMNs does not appear to involve SP-A's lectin domain. These data suggest that the pulmonary collectins SP-A and SP-D facilitate the resolution of inflammation by accelerating apoptotic PMN clearance.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Schagat
authors.forename: J A
authors.initials: JA
authors.lastname: Wofford
authors.forename: J R
authors.initials: JR
authors.lastname: Wright
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002352:Carrier Proteins / Q000502:physiology; D037222:Collectins; D015922:Complement C1q / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology; D006031:Glycosylation; D006358:Hot Temperature; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000166:cytology* / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D009895:Opsonin Proteins / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; D037222:Collectins; D006023:Glycoproteins; D008024:Ligands; D009895:Opsonin Proteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D015922:Complement C1q; D009195:Peroxidase