SURFACTANT PROTEIN-A REDUCES BINDING AND PHAGOCYTOSIS OF PNEUMOCYSTIS-CARINII BY HUMAN ALVEOLAR MACROPHAGES IN-VITRO

Surfactant protein-A (SP-A) levels are increased in Pneumocystis carin ii pneumonia. but the role of SP-A in the pathogenesis of P. carinii p neumonia is not completely understood. This study investigated the eff ect of SP-A on the in vitro binding and phagocytosis of P. carinii by normal human alveolar macrophages (AM). Determination of binding and p hagocytosis was done with a fluorescence-based assay, utilizing fluore scein isothiocyanate (FITC)-labeled P. carinii. Binding and phagocytos is of P. carinii to AM correlated inversely with the levels of SP-A pr esent on the surface of the organisms (r = -0.6323, P = 0.0086; and r = -0.9837, P < 0.0001, respectively). The addition of exogenous SP-A t o organisms with low surface-associated SP-A reduced P. carinii bindin g by 30% (P < 0.05) and reduced phagocytosis by 20% (P < 0.05), wherea s this effect was reversed with ethylenediamine tetraacetic acid (EDTA ) or anti-SP-A antibody. Furthermore, binding and phagocytosis were en hanced 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 phagocyto sis reflected binding of SP-A to the organisms rather than a direct ef fect of SP-A on the macrophages. These data suggest that increased lev els of SP-A may contribute to the pathogenesis of P. carinii pneumonia through binding to the surface of the organism and interfering with A M recognition of this opportunistic pulmonary pathogen.