Guo W X, Ghebrehiwet B, Weksler B, Schweitzer K, Peerschke E I
Department of Pathology, and Medicine, The Joan and Sanford I. Weill College of Medicine of Cornell University, New York, New York, USA.
J Lab Clin Med. 1999 Jun;133(6):541-50. doi: 10.1016/s0022-2143(99)90183-x.
Endothelial cells express a variety of receptor systems involved in humoral defense, including receptors for the collagen-like and globular domains of the complement component C1q, designated cC1qR and gC1qR, respectively. In the present study a microvascular endothelial cell line was used to test the hypothesis that expression of these C1q-binding proteins may be affected by vascular inflammatory reactions. The results demonstrate that the expression of both cC1qR and gC1qR by bone marrow vascular endothelial cells is up-regulated by inflammatory mediators, interferon-gamma, tumor necrosis factor-alpha, and lipopolysaccharide (Escherichia coli, 055:B5) in a dose- and time-dependent manner, as detected by enzyme-linked immunosorbent assay. cC1qR and gC1qR expression increased significantly (P < .05) within 4 to 7 hours and doubled after 22 hours of stimulation. 3H-thymidine incorporation studies and direct cell counts confirmed that increased C1qR expression was not due to increased cell proliferation. Northern blot analysis revealed that the up-regulation of cC1qR and gC1qR protein expression was preceded by increases in corresponding mRNA levels, suggesting increased gene transcription. Indeed C1qR mRNA up-regulation was prevented by actinomycin D, and C1qR protein synthesis was inhibited by cycloheximide. Bone marrow vascular endothelial cell exposure to C1q, however, did not alter cC1qR or gC1qR expression, but up-regulation of the leukocyte adhesion molecule ICAM-1 was noted in the presence of aggregated C1q. The up-regulation of C1qR by inflammatory mediators and the ability of C1q itself to increase ICAM-1 expression suggest a potential role for these binding sites in vascular inflammation and immune injury.
内皮细胞表达多种参与体液防御的受体系统，包括补体成分C1q的胶原样结构域和球形结构域的受体，分别命名为cC1qR和gC1qR。在本研究中，使用一种微血管内皮细胞系来检验这些C1q结合蛋白的表达可能受血管炎症反应影响这一假说。结果表明，通过酶联免疫吸附测定法检测，骨髓血管内皮细胞的cC1qR和gC1qR表达均被炎性介质、干扰素-γ、肿瘤坏死因子-α和脂多糖（大肠杆菌，055:B5）以剂量和时间依赖性方式上调。cC1qR和gC1qR表达在4至7小时内显著增加（P < 0.05），刺激22小时后增加一倍。3H-胸腺嘧啶核苷掺入研究和直接细胞计数证实，C1qR表达增加并非由于细胞增殖增加。Northern印迹分析显示，cC1qR和gC1qR蛋白表达上调之前，相应的mRNA水平增加，提示基因转录增加。事实上，放线菌素D可阻止C1qR mRNA上调，环己酰亚胺可抑制C1qR蛋白合成。然而，骨髓血管内皮细胞暴露于C1q并不会改变cC1qR或gC1qR表达，但在存在聚集的C1q时，白细胞黏附分子ICAM-1的表达上调。炎性介质对C1qR的上调作用以及C1q本身增加ICAM-1表达的能力表明，这些结合位点在血管炎症和免疫损伤中可能发挥潜在作用。
