IGM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo
IGM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo
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DOI：
10.1080/08916930500124452
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发表时间：
2005-06-01
期刊：
影响因子：
3.5
通讯作者：
Elkon, KB
中科院分区：
文献类型：
--
作者：
Ogden, CA;Kowalewski, R;Elkon, KB
多种补体成分已在凋亡细胞中被检测到，并被提出促进吞噬细胞的识别和/或摄入。补体激活的触发因素仍然不确定。为了确定IgM在体外和体内经典通路激活和凋亡细胞清除中的作用，我们在血清IgM （sIgM）缺乏的小鼠中量化了这些参数。sIgM缺失血清培养的凋亡细胞，其骨髓源性巨噬细胞的吞噬能力明显降低，与体外C1q缺失血清培养的凋亡细胞相似。同样，与野生型小鼠相比，sIgM缺乏小鼠的腹腔内凋亡细胞清除率和细胞C3沉积显著降低。清除和C3沉积通过IgM的补充重建。在sIgM和C1q均缺乏的小鼠中，需要添加两种血清因子才能恢复清除。这些研究结果在定量的基础上表明，sIgM是凋亡细胞腹腔吞噬所需的有效因子，并进一步证明IgM和C1q协同激活补体，导致C3沉积在凋亡细胞表面，最终被巨噬细胞有效清除凋亡细胞。
A variety of complement components have been detected on apoptotic cells and proposed to facilitate recognition and/or ingestion by phagocytes. The triggers for complement activation remain uncertain. To determine the role of IgM in classical pathway activation and clearance of apoptotic cells in vitro and in vivo, we quantified these parameters in mice deficient in serum IgM (sIgM). Phagocytosis by bone marrow-derived macrophages of apoptotic cells incubated with serum deficient in sIgM was markedly reduced, similar to apoptotic cells incubated with C1q deficient serum in vitro. Similarly, intraperitoneal clearance of apoptotic cells and cellular C3 deposition were significantly reduced in mice deficient in sIgM compared to wildtype mice. Clearance and C3 deposition were reconstituted by addback of IgM. In mice deficient in both sIgM and C1q, addback of both serum factors was required for restoration of clearance. These findings indicate that, on a quantitative basis, sIgM is a potent factor required for intraperitoneal phagocytosis of apoptotic cells, and further demonstrate that IgM and C1q work in concert to activate complement, resulting in C3 deposition on the apoptotic cell surface and ultimately, efficient clearance of the apoptotic cell by macrophages.