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

Microglial activation has been associated with several degenerative diseases of the central nervous system (CNS), One consequence of activation is the induction of a more efficient phagocytic response, and it is therefore important to determine what factors regulate microglial phagocytosis and whether this capacity influences the progression of neurodegenerative changes. Previous studies have demonstrated that complement component Clq enhances Pc receptor- and CR1-mediated phagocytosis in cells of the myeloid lineage via 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 phagocytosis. Neonatal rat microglia were shown to express C1qR(P) as assessed by flow cytometry and immunocytochemistry, Interaction of these cells with substrate-bound Clq was shown to enhance both FcR- and CR1-mediated phagocytosis two- to fourfold. In addition, introduction of an antibody raised against the carboxy-terminal, cytoplasmic domain of C1qR(P) into microglia by electroporation 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).