Complement-dependent clearance of apoptotic cells by human macrophages.
Complement-dependent clearance of apoptotic cells by human macrophages.
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DOI：
10.1084/jem.188.12.2313
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发表时间：
1998-12-21
期刊：
影响因子：
--
通讯作者：
Elkon KB
中科院分区：
文献类型：
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作者：
Mevorach D;Mascarenhas JO;Gershov D;Elkon KB
凋亡细胞会被吞噬细胞迅速吞噬，但导致这一现象的受体和配体的特征还不完全。以前所描述的血液来源的巨噬细胞上的受体的特征是在没有血清的情况下，并且显示相对较低的对凋亡细胞的摄取。在吞噬试验中加入血清，可使对凋亡细胞的摄取增加三倍以上。负责增强摄取的血清因子被确定为补体成分，需要激活经典途径和替代途径扩增环。磷脂酰丝氨酸暴露在凋亡细胞表面是补体激活的部分原因，并导致在凋亡细胞表面覆盖C3bi。在有血清存在的情况下，C3bi的巨噬细胞受体CR3(CD11b/CD18)和CR4(CD11c/CD18)与先前描述的与清除有关的受体相比，在摄取凋亡细胞方面明显更有效。补体激活可能是在体循环中有效吸收凋亡细胞所必需的，早期成分缺陷可能通过增加对凋亡细胞的暴露和/或异常沉积而易于发生全身性自身免疫。
Apoptotic cells are rapidly engulfed by phagocytes, but the receptors and ligands responsible for this phenomenon are incompletely characterized. Previously described receptors on blood- derived macrophages have been characterized in the absence of serum and show a relatively low uptake of apoptotic cells. Addition of serum to the phagocytosis assays increased the uptake of apoptotic cells by more than threefold. The serum factors responsible for enhanced uptake were identified as complement components that required activation of both the classical pathway and alternative pathway amplification loop. Exposure of phosphatidylserine on the apoptotic cell surface was partially responsible for complement activation and resulted in coating the apoptotic cell surface with C3bi. In the presence of serum, the macrophage receptors for C3bi, CR3 (CD11b/CD18) and CR4 (CD11c/CD18), were significantly more efficient in the uptake of apoptotic cells compared with previously described receptors implicated in clearance. Complement activation is likely to be required for efficient uptake of apoptotic cells within the systemic circulation, and early component deficiencies could predispose to systemic autoimmunity by enhanced exposure to and/or aberrant deposition of apoptotic cells.