Webster S D, Park M, Fonseca M I, Tenner A J
Department of Molecular Biology and Biochemistry, University of California, Irvine 92697, USA.
J Leukoc Biol. 2000 Jan;67(1):109-16. doi: 10.1002/jlb.67.1.109.
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.
小胶质细胞激活与中枢神经系统（CNS）的几种退行性疾病有关。激活的一个后果是诱导更有效的吞噬反应，因此确定哪些因素调节小胶质细胞吞噬作用以及这种能力是否影响神经退行性变化的进展很重要。先前的研究表明，补体成分C1q通过细胞表面受体C1qRp增强髓系谱系细胞中Fc受体和CR1介导的吞噬作用。由于在几种退行性CNS疾病的病变区域发现了C1q，因此进行了当前的研究以表征C1q对小胶质细胞吞噬作用的影响。通过流式细胞术和免疫细胞化学评估，新生大鼠小胶质细胞显示表达C1qRp。这些细胞与底物结合的C1q的相互作用显示可将FcR和CR1介导的吞噬作用增强两到四倍。此外，通过电穿孔将针对C1qRp羧基末端胞质结构域产生的抗体引入小胶质细胞，显著降低了C1q增强IgG包被靶标摄取的能力，而非特异性IgG则没有这种作用。这些结果表明，活跃退变区域的C1q可能通过与小胶质细胞C1qRp相互作用来促进小胶质细胞的吞噬能力。
