Am. J. Respir. Cell Mol. Biol., Volume 18, Number 6, June, 1998 834-843

Surfactant Protein-A Reduces Binding and Phagocytosis of Pneumocystis carinii by Human Alveolar Macrophages In Vitro

Henry Koziel, David S. Phelps, Jay A. Fishman, Martine Y. K. Armstrong, Frank F. Richards, and Richard M. Rose

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston; Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; and MacArthur Center for Molecular Parasitology, Yale University School of Medicine, New Haven, Connecticut

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.

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