Bohlson Suzanne S, Fraser Deborah A, Tenner Andrea J
Department of Molecular Biology and Biochemistry, Center for Immunology, University of California, Irvine, CA 92697, USA.
Mol Immunol. 2007 Jan;44(1-3):33-43. doi: 10.1016/j.molimm.2006.06.021. Epub 2006 Aug 14.
C1q and mannose binding lectin, members of the "defense collagen" family, are pattern recognition molecules that can trigger rapid enhanced phagocytosis resulting in efficient containment of pathogens or clearance of cellular debris, apoptotic cells and immune complexes. In addition, interaction of C1q and mannose binding lectin with the phagocyte alters subsequent phagocyte cytokine synthesis, and thus may have important implications in directing acute inflammation as well as long-term protective immunity. The importance of the role of defense collagens in phagocytosis of apoptotic cells is highlighted by studies in vivo of mice deficient in C1q, pulmonary surfactant D and mannose binding lectin in which there is delayed clearance of apoptotic cells. Indeed, deficiency of C1q is a risk factor for the development of autoimmunity in both humans and mice, consistent with the hypothesis that inefficient clearance of apoptotic cells results in release of autoantigens and contributes to the pathology associated with autoimmune diseases such as systemic lupus erythematosus. Further understanding of the importance of C1q and mannose binding lectin in the clearance of apoptotic cells and regulation of cytokine synthesis and identification of the receptors implicated in mediating these processes should provide novel targets for therapeutic intervention in the control and manipulation of the immune response in terms of both host defense against infectious disease and tissue repair and remodeling.
C1q和甘露糖结合凝集素是“防御性胶原蛋白”家族的成员,它们是模式识别分子,能够引发快速增强的吞噬作用,从而有效地遏制病原体或清除细胞碎片、凋亡细胞和免疫复合物。此外,C1q和甘露糖结合凝集素与吞噬细胞的相互作用会改变随后吞噬细胞细胞因子的合成,因此可能在指导急性炎症以及长期保护性免疫方面具有重要意义。体内对缺乏C1q、肺表面活性物质D和甘露糖结合凝集素的小鼠进行的研究突出了防御性胶原蛋白在凋亡细胞吞噬作用中的重要性,这些小鼠体内凋亡细胞的清除存在延迟。事实上,C1q缺乏是人类和小鼠自身免疫性疾病发生的一个危险因素,这与凋亡细胞清除效率低下导致自身抗原释放并促成与自身免疫性疾病(如系统性红斑狼疮)相关的病理过程这一假说相一致。进一步了解C1q和甘露糖结合凝集素在凋亡细胞清除以及细胞因子合成调节中的重要性,并确定参与介导这些过程的受体,应该能够为在宿主抵御传染病以及组织修复和重塑方面控制和操纵免疫反应提供新的治疗干预靶点。