C-reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatoryinnate immune response: Implications for systemic autoimmunity

C-reactive protein (CRP) is a serum protein that is massively induced as pa rt of the innate immune response to infection and tissue injury. As CRP has been detected in damaged tissues and is known to activate complement, we a ssessed whether apoptotic lymphocytes bound CRP and determined the effect o f binding on innate immunity. CRP bound to apoptotic cells in a Ca2+-depend ent manner and augmented the classical pathway of complement activation but protected the cells from assembly of the terminal complement components. F urthermore, CRP enhanced opsonization and phagocytosis of apoptotic cells b y macrophages associated with the expression of the antiinflammatory cytoki ne transforming growth factor beta. The antiinflammatory effects of CRP req uired Clq and factor H and were not effective once cells had become necroti c. These observations demonstrate that CRP and the classical complement com ponents act in concert to promote noninflammatory clearance of apoptotic ce lls and may help to explain how deficiencies of the classical pathway and c ertain pentraxins lead to impaired handling of apoptotic cells and increase d necrosis with the likelihood of immune response to self.