Functions associated with the C1q receptor.

Abstract

Information gathered from various sources indicates that the receptor for human C1q is expressed on a wide range of normal and cultured cell lines. Similarly, the functions mediated by the C1qR are as diverse as the cells that express the molecule. On B lymphocytes, for instance, the C1qR is known to mediate cellular cytotoxicity, induce an anti-proliferative response, inhibit synthesis of IL-1 and modulate the synthesis of Ig, whereas on PMNs and monocytes the C1qR participates in the increase of oxidative metabolism and enhancement of phagocytosis of opsonized target particles. Endothelial cells which form an important barrier between blood and vascular basement membrane use their C1qR to localize C1q bearing immune complexes into the basement membrane and thus initiate an inflammatory response. Human diploid fibroblasts express two types of C1qRs: a low affinity C1qR for the collagen-like domain and a small subpopulation expressing high affinity C1qR which binds to the globular region of C1q. Since the high affinity subpopulation manifests characteristics of fibroblasts participating in wound healing and tissue regeneration, the C1qR on these cells may play an important role at sites of inflammation. Recently, binding of C1q to the C1qR on mouse fibroblasts was shown to induce chemotaxis and K+ conductance activation with an increase in cytosolic Ca2+. Although isolation of C1qR from every cell type has not been accomplished as yet, partial characterization of highly purified C1qR from Raji cells and platelets indicate that at least on these cell types, the structure of the molecule is similar. Both molecules are anionic, single chain glycoproteins of approximately 67-70 kDA and upon reduction on SDS-PAGE migrate to an apparent 80-85 kDa indicative of the presence of disulfide bonds. The sedimentation coefficient was estimated to be 2.4-4.2S for platelet C1qR and 4.2S for that of Raji. Equilibrium isoelectric focusing showed the Raji cell C1qR to migrate with a pI of 5.5-6.0. Because the Raji C1qR reveals two components when analyzed by two dimensional SDS-PAGE, the possibility that the C1qR may be a doublet of two apparent 70 kDa molecules only one of which contains relatively more intrachain disulfide bonds is being raised.