Weyer C, Sabat R, Wissel H, Krüger D H, Stevens P A, Prösch S
Departments of Virology, Medical Immunology, and Neonatology, Humboldt University, Medical School (Charité), Berlin, Germany.
Am J Respir Cell Mol Biol. 2000 Jul;23(1):71-8. doi: 10.1165/ajrcmb.23.1.3859.
The role of surfactant protein (SP)-A in cytomegalovirus (CMV) infection of the lung was investigated. We found that SP-A binds to various immobilized human CMV proteins and those exposed on the surface of infected embryonal lung fibroblasts. The interaction between SP-A and immobilized CMV proteins was found to be calcium-dependent and inhibited by mannan, suggesting involvement of the carbohydrate recognition domain of SP-A and high-mannose carbohydrate residues of viral envelope glycoproteins. Using flow cytometry and confocal laser fluorescence microscopy in the rat model we showed that preincubation of rat CMV with SP-A stimulates its binding and internalization by rat type II pneumocytes and alveolar tissue macrophages. This effect was concentration- and Ca(2+)-dependent but was not inhibited by mannan. Therefore, the domains of SP-A involved in SP-A CMV interaction and in interaction of the SP-A/virus complex with rat lung cells are distinct. Additionally, in the human CMV model, sheep as well as human proteinosis SP-A did not significantly affect human CMV replication in embryonal lung fibroblasts. Thus, SP-A may contribute to CMV-associated pathology of the lung by increasing the efficiency of target cell infection.
研究了表面活性蛋白（SP）-A在巨细胞病毒（CMV）肺部感染中的作用。我们发现SP-A可与多种固定化的人CMV蛋白以及感染的胚胎肺成纤维细胞表面暴露的蛋白结合。发现SP-A与固定化CMV蛋白之间的相互作用是钙依赖性的，并被甘露聚糖抑制，这表明SP-A的碳水化合物识别结构域和病毒包膜糖蛋白的高甘露糖碳水化合物残基参与其中。在大鼠模型中使用流式细胞术和共聚焦激光荧光显微镜，我们发现用SP-A预孵育大鼠CMV可刺激其与大鼠II型肺细胞和肺泡组织巨噬细胞的结合及内化。这种作用是浓度和Ca(2+)依赖性的，但不受甘露聚糖抑制。因此，参与SP-A与CMV相互作用以及SP-A/病毒复合物与大鼠肺细胞相互作用的SP-A结构域是不同的。此外，在人CMV模型中，绵羊和人蛋白样SP-A对胚胎肺成纤维细胞中的人CMV复制没有显著影响。因此，SP-A可能通过提高靶细胞感染效率而导致CMV相关的肺部病理改变。
