Yuste Jose, Botto Marina, Bottoms Stephen E, Brown Jeremy S
Centre for Respiratory Research, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, London, United Kingdom.
PLoS Pathog. 2007 Sep 28;3(9):1208-19. doi: 10.1371/journal.ppat.0030120.
The physiological functions of the acute phase protein serum amyloid P (SAP) component are not well defined, although they are likely to be important, as no natural state of SAP deficiency has been reported. We have investigated the role of SAP for innate immunity to the important human pathogen Streptococcus pneumoniae. Using flow cytometry assays, we show that SAP binds to S. pneumoniae, increases classical pathway-dependent deposition of complement on the bacteria, and improves the efficiency of phagocytosis. As a consequence, in mouse models of infection, mice genetically engineered to be SAP-deficient had an impaired early inflammatory response to S. pneumoniae pneumonia and were unable to control bacterial replication, leading to the rapid development of fatal infection. Complement deposition, phagocytosis, and control of S. pneumoniae pneumonia were all improved by complementation with human SAP. These results demonstrate a novel and physiologically significant role for SAP for complement-mediated immunity against an important bacterial pathogen, and provide further evidence for the importance of the classical complement pathway for innate immunity.
急性期蛋白血清淀粉样蛋白P（SAP）成分的生理功能尚未完全明确，尽管其功能可能很重要，因为目前尚无SAP缺乏自然状态的报道。我们研究了SAP在针对重要人类病原体肺炎链球菌的天然免疫中的作用。通过流式细胞术分析，我们发现SAP可结合肺炎链球菌，增加补体在细菌上经典途径依赖性沉积，并提高吞噬作用效率。因此，在感染小鼠模型中，经基因工程改造而缺乏SAP的小鼠对肺炎链球菌肺炎的早期炎症反应受损，无法控制细菌复制，导致致命感染迅速发展。用人SAP进行补充可改善补体沉积、吞噬作用以及对肺炎链球菌肺炎的控制。这些结果证明了SAP在补体介导的针对重要细菌病原体免疫中的新的生理重要作用，并为经典补体途径对天然免疫的重要性提供了进一步证据。
