Navratil J S, Watkins S C, Wisnieski J J, Ahearn J M
Immunology Graduate Training Program, Departments of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
J Immunol. 2001 Mar 1;166(5):3231-9. doi: 10.4049/jimmunol.166.5.3231.
Complement protein C1q is required to maintain immune tolerance. The molecular mechanism responsible for this link has not been determined. We have previously demonstrated that C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes, suggesting that it may participate in clearance of self Ags generated during programmed cell death. Here, we demonstrate that C1q also binds directly to apoptotic blebs of vascular endothelial cells and PBMC. These apoptotic cells are recognized by the globular heads of C1q, which bind specifically to the surface blebs, and deposition increases as the blebs mature on the cell surface. These observations suggest that C1q may participate in the clearance of apoptotic cells from the circulation and from the walls of the vascular lumen. The interaction of surface blebs with the globular heads of C1q suggests that surface blebs may be capable of directly activating the classical pathway of complement under certain circumstances, generating C4- and C3-derived ligands for receptors such as CR1, CR2, CR3, and CR4. Appropriate recognition of apoptotic cells by C1q and targeted clearance of the molecular contents of surface blebs to complement receptors may be critical for the maintenance of immune tolerance.
补体蛋白C1q是维持免疫耐受所必需的。负责这种联系的分子机制尚未确定。我们之前已经证明，C1q直接且特异性地结合凋亡人角质形成细胞的表面泡，这表明它可能参与程序性细胞死亡过程中产生的自身抗原的清除。在此，我们证明C1q也直接结合血管内皮细胞和外周血单个核细胞的凋亡泡。这些凋亡细胞被C1q的球形头部识别，球形头部特异性地结合到表面泡上，并且随着泡在细胞表面成熟，沉积增加。这些观察结果表明，C1q可能参与从循环系统和血管腔壁清除凋亡细胞。表面泡与C1q球形头部的相互作用表明，在某些情况下，表面泡可能能够直接激活补体的经典途径，产生用于CR1、CR2、CR3和CR4等受体的C4和C3衍生配体。C1q对凋亡细胞的适当识别以及将表面泡的分子内容物靶向清除至补体受体对于维持免疫耐受可能至关重要。
