Koziel H, Phelps D S, Fishman J A, Armstrong M Y, Richards F F, Rose R M
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Am J Respir Cell Mol Biol. 1998 Jun;18(6):834-43. doi: 10.1165/ajrcmb.18.6.3059.
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.
卡氏肺孢子虫肺炎患者的表面活性蛋白A（SP-A）水平升高，但SP-A在卡氏肺孢子虫肺炎发病机制中的作用尚未完全明确。本研究调查了SP-A对正常人肺泡巨噬细胞（AM）体外结合和吞噬卡氏肺孢子虫的影响。采用基于荧光的检测方法，利用异硫氰酸荧光素（FITC）标记的卡氏肺孢子虫来测定结合和吞噬情况。卡氏肺孢子虫与AM的结合及吞噬与生物体表面存在的SP-A水平呈负相关（r分别为-0.6323，P = 0.0086；以及r = -0.9827，P < 0.0001）。向表面相关SP-A水平低的生物体添加外源性SP-A可使卡氏肺孢子虫的结合减少30%（P < 0.05），吞噬减少20%（P < 0.05），而乙二胺四乙酸（EDTA）或抗SP-A抗体可逆转这种作用。此外，酶法去除卡氏肺孢子虫表面相关的SP-A后，结合和吞噬增强，添加外源性SP-A可逆转这种作用。观察到的SP-A对卡氏肺孢子虫结合和吞噬的抑制作用反映了SP-A与生物体的结合，而非SP-A对巨噬细胞的直接作用。这些数据表明，SP-A水平升高可能通过与生物体表面结合并干扰AM对这种机会性肺部病原体的识别，从而促进卡氏肺孢子虫肺炎的发病机制。
