Structural and functional evidence for microglial expression of C1qR(p), the C1q receptor that enhances phagocytosis

Microglial activation has been associated with several degenerative disease s of the central nervous system (CNS), One consequence of activation is the induction of a more efficient phagocytic response, and it is therefore imp ortant to determine what factors regulate microglial phagocytosis and wheth er this capacity influences the progression of neurodegenerative changes. P revious studies have demonstrated that complement component Clq enhances Pc receptor- and CR1-mediated phagocytosis in cells of the myeloid lineage vi a a cell surface receptor, C1qR(P). Because Clq has been found in the area of lesions in several degenerative CNS diseases, the current investigations were carried out to characterize the effects of Clq on microglial phagocyt osis. Neonatal rat microglia were shown to express C1qR(P) as assessed by f low cytometry and immunocytochemistry, Interaction of these cells with subs trate-bound Clq was shown to enhance both FcR- and CR1-mediated phagocytosi s two- to fourfold. In addition, introduction of an antibody raised against the carboxy-terminal, cytoplasmic domain of C1qR(P) into microglia by elec troporation markedly diminished the ability of Clq to enhance uptake of IgG -coated targets, whereas nonspecific IgG had no such effect. These results suggest that Clq in areas of active degeneration may promote the phagocytic capacity of microglia via interaction with microglial C1qR(P).