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 C1q enhances Fc receptor- and CR1-mediated phagocytosis in cells of the myeloid lineage via a cell surface receptor, C1qRp. 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 C1qRp, as assessed by flow cytometry and immunocytochemistry. Interaction of these cells with substrate-bound C1q 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 C1qRp 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 C1qRp.
Webster
S D
SD
Department of Molecular Biology and Biochemistry, University of California, Irvine 92697, USA. swebster@uci.edu
Park
M
M
Fonseca
M I
MI
Tenner
A J
AJ
D000818:Animals; D002352:Carrier Proteins; D002478:Cells, Cultured; D003166:Complement Activating Enzymes / Q000502:physiology; D015922:Complement C1q / Q000502:physiology; D006801:Humans; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins / Q000502:physiology; D017628:Microglia / Q000502:physiology*; D024101:Mitochondrial Proteins; D010587:Phagocytosis; D051381:Rats; D011951:Receptors, Complement / Q000502:physiology*
C087299:C1QBP protein, human; C490195:C1qbp protein, rat; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D015922:Complement C1q; D003166:Complement Activating Enzymes