APOPTOSIS AND COMPLEMENT-STUDIES ON THE MECHANISM OF COMPKEMENT ACTIVATION AND THE BIOLOGICAL SIGNIFICANCE

我们研究了凋亡细胞激活自体补体的机制以及补体激活在巨噬细胞清除凋亡细胞中的生物学意义。 1．凋亡细胞中自体补体途径的激活剂。同源活细胞上不会发生补体激活。我们观察到人凋亡细胞对自体补体途径的激活，表明在凋亡细胞上出现了新型补体激活剂。为了表征新型激活剂，使 Jurkat Y 细胞系凋亡，对其细胞蛋白进行 SDS-PAGE，随后用人血清作为补体来源进行处理。补体激活发生在 50 KDa 蛋白上，该蛋白与 C3b 一起沉积，表明存在能够激活自体补体的 50 KDa 分子。在活细胞的膜部分中检测到相同的分子。基于这些数据，我们提出50 KDa激活蛋白位于活细胞的膜部分，并在凋亡时暴露于细胞表面。目前正在对新型补体激活蛋白的分离进行研究。2．补体激活对巨噬细胞吞噬凋亡细胞的影响。我们发现血清处理的凋亡细胞被 ic3b 标记，ic3b 被称为调理素。这表明凋亡细胞上的ic3b可能与巨噬细胞的CR3相互作用，促进凋亡细胞的吞噬作用。发现ic3b包被的凋亡细胞比未包被ic3b的细胞被巨噬细胞吞噬的速度要快得多。抗ic6b抗体和抗ic6b抗体可以抑制巨噬细胞对ic6b包被的凋亡细胞的吞噬作用。抗CR3，表明凋亡细胞上的ic3b应与巨噬细胞上的CR3相互作用，促进吞噬细胞对凋亡细胞的清除。因此，补体不仅是宿主的防御系统，也是清除不必要的细胞（例如凋亡细胞）的生理系统。较少的

We investigated the mechanism of autologous complement activation by apoptotic cells and biological significance of complement activation in the clearance of apoptotic cells by macrophages.1. Activator of the autologous complement pathway in apoptotic cells. Complement activation does not occur on homologous live cells.We observed the activation of the autologous complement pathway by human apoptotic cells, suggesting the appearance of a novel complement activator on apoptotic cells.To characterize the novel activator, Jurkat Y cell line was allowed to spoptosis and its cell proteins were subjected to SDS-PAGE and subsequently treated with human serum as a source of complement.Complemnt activation occurred on a 50 KDa protein, which was become deposited with C3b, suggesting the presence of 50 KDa molecule capable of activating autologous complement.The same molecule was detected in the membrane fraction of live cells. Based on these data, we proposed that the 50 KDa activator protein i … More s located in the membrane fraction of live cells and become exposed to cell surface upon apoptosis.Studies on the isolation of the novel complement activator are now in progress.2. The effect of complement activation upon phagocytosis of qpoptotic cells by macrophages.We found that serum-treated apoptotic cells were labeled with ic3b, which is known as an opsonin. This suggested that ic3b on apoptotic cells might interact with CR3 of macrophages and promote the phagocytosis of apoptotic cells.The ic3b-coated apoptotic cells were found to be phagocytosed much more quickly than ic3b-noncoated cells by macrophages.The phagocytosis of ic6b-coated apoptotic cells by macrophages was found to be inhibited by anti-ic6b antibodies and anti-CR3, indicating that ic3b on apoptotic cells should interact with CR3 on macrophages and promote the clearance of apoptotic cells by phagocytes.Thus, complement is not only a host defense system but also a physiological system to remove unnecessary cells, such as apoptotic cells. Less