title: Surfactant protein-A reduces binding and phagocytosis of pneumocystis carinii by human alveolar macrophages in vitro.
abstract: Surfactant protein-A (SP-A) levels are increased in Pneumocystis carinii pneumonia, but the role of SP-A in the pathogenesis of P. carinii pneumonia is not completely understood. This study investigated the effect of SP-A on the in vitro binding and phagocytosis of P. carinii by normal human alveolar macrophages (AM). Determination of binding and phagocytosis was done with a fluorescence-based assay, utilizing fluorescein isothiocyanate (FITC)-labeled P. carinii. Binding and phagocytosis of P. carinii to AM correlated inversely with the levels of SP-A present on the surface of the organisms (r = -0.6323, P = 0.0086; and r = -0.9827, P < 0.0001, respectively). The addition of exogenous SP-A to organisms with low surface-associated SP-A reduced P. carinii binding by 30% (P < 0.05) and reduced phagocytosis by 20% (P < 0.05), whereas this effect was reversed with ethylenediamine tetraacetic acid (EDTA) or anti-SP-A antibody. Furthermore, binding and phagocytosis were enhanced after enzymatic removal of P. carinii surface-associated SP-A, and this effect was reversed with the addition of exogenous SP-A. The observed inhibitory effect of SP-A on P. carinii binding and phagocytosis reflected binding of SP-A to the organisms rather than a direct effect of SP-A on the macrophages. These data suggest that increased levels of SP-A may contribute to the pathogenesis of P. carinii pneumonia through binding to the surface of the organism and interfering with AM recognition of this opportunistic pulmonary pathogen.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. hkoziel@west.bidmc.harvard.edu
authors.forename: H
authors.initials: H
authors.lastname: Koziel
authors.forename: D S
authors.initials: DS
authors.lastname: Phelps
authors.forename: J A
authors.initials: JA
authors.lastname: Fishman
authors.forename: M Y
authors.initials: MY
authors.lastname: Armstrong
authors.forename: F F
authors.initials: FF
authors.lastname: Richards
authors.forename: R M
authors.initials: RM
authors.lastname: Rose
mesh_terms: D002176:Candida albicans / Q000378:metabolism; D002478:Cells, Cultured; D004492:Edetic Acid / Q000494:pharmacology; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006867:Hydrolases / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D011010:Pneumocystis / Q000378:metabolism*; D011510:Proteolipids / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D006023:Glycoproteins; D007074:Immunoglobulin G; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C037833:zymolyase; D004492:Edetic Acid; D006867:Hydrolases