Structural and functional evidence for microglial expression of C1qRP, the C1q receptor that enhances phagocytosis

Abstract

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 C1q enhances Fc receptor-and CR1-mediated phagocytosis in cells of the myeloid lineage via a cell surface receptor, C1qR P . Because C1q has been found in the area of lesions in several degenerative CNS diseases, the current investigations were carried out to characterize the effects of C1q 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 C1q was shown to enhance both FcRand 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 C1q to enhance uptake of IgG-coated targets, whereas nonspecific IgG had no such effect. These results suggest that C1q in areas of active degeneration may promote the phagocytic capacity of microglia via interaction with microglial C1qR P . J. Leukoc. Biol. 67: 109-116; 2000.

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

“…74 Phagocytosis of cellular targets, such as invading microbes and apoptotic cells, is enhanced if coated (opsonized) with complement including C1q. 75,76 Interestingly, increased deposition of C1q has been described in a group of autism patients with gastrointestinal symptoms, in which enhanced deposition of C1q was detected on intestinal epithelial cells and was co-localized with IgG. 77 This finding suggests that a C1q-antibody driven lytic response directed against a potential self-antigen in the intestinal cells, which could perturb the barrier functioning of the intestine, may be important in this subgroup of patients with autism.…”

CD93 Is Rapidly Shed from the Surface of Human Myeloid Cells and the Soluble Form Is Detected in Human Plasma

“…The polyclonal anti-CD93 cytoplasmic tail Ab 1150 was generated against the C-terminal 11 aa of CD93 as previously described (21). Polyclonal anti-CD93 1157 was generated by immunization with sCD93 produced in insect SF9 cells as previously described (16).…”

Regulating Factors for Microglial Activation.

“…40) C1q modulates the phagocytotic activity of microglia. Two controversial roles of C1q have been reported: C1q enhances phagocytosis of Ab 41) and inhibits it. 42) 3.2.3.…”