补体成分 C1q 通过在血管外膜成纤维细胞和血管平滑肌细胞中 C1q 球状头部的受体引发外在凝血途径。
Complement component C1q initiates extrinsic coagulation via the receptor for the globular head of C1q in adventitial fibroblasts and vascular smooth muscle cells.
机构信息
Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA.
Department of Medicine, Stony Brook University, Stony Brook, New York, USA.
出版信息
Immun Inflamm Dis. 2023 Jan;11(1):e769. doi: 10.1002/iid3.769.
BACKGROUND
Vascular diseases are highly associated with inflammation and thrombosis. Elucidating links between these two processes may provide a clearer understanding of these diseases, allowing for the design of more effective treatments. The activation of complement component 1 (C1) is a crucial contributor to innate immunity and is associated with significant concentrations of circulating C1q. Many pathological pathways initiate when C1q interacts with gC1qR. This interaction plays a major role in inflammation observed during atherosclerosis and the initiation of intrinsic coagulation. However, the effects of C1 and the role of C1q/gC1qR on extrinsic coagulation, which is the more physiologically relevant coagulation arm, has not been studied. We hypothesized that C1q binding to gC1qR enhances the expression of tissue factor (TF) in adventitial fibroblasts and vascular smooth muscle cells, the primary TF bearing cells in the body.
METHODS
Using an enzyme-linked immunosorbent assay approach, TF expression and the role of gC1qR was observed. Cells were conditioned for 1 h with C1q or a gC1qR blocker and C1q, to assess the role of gC1qR. Additionally, cell growth characteristics were monitored to assess changes in viability and metabolic activity.
RESULTS
Our results indicate that the expression of TF increased significantly after incubation with C1q as compared with unconditioned cells. Cells conditioned with gC1qR blockers and C1q exhibited no change in TF expression when compared with cells conditioned with the blocking antibodies alone. Our results show no significant differences in metabolic activity or cell viability under these conditions.
CONCLUSIONS
This indicates that gC1qR association with C1q induces TF expression and may initiate extrinsic coagulation. Overall, this data illustrates a role for C1q in the activation of extrinsic coagulation and that gC1qR activity may link inflammation and thrombosis.
背景
血管疾病与炎症和血栓形成高度相关。阐明这两个过程之间的联系可以更清楚地了解这些疾病，从而设计更有效的治疗方法。补体成分 1（C1）的激活是先天免疫的关键贡献者，与循环 C1q 的显著浓度相关。许多病理途径在 C1q 与 gC1qR 相互作用时开始。这种相互作用在动脉粥样硬化和内在凝血起始时观察到的炎症中起着主要作用。然而，C1 的作用以及 C1q/gC1qR 对体外凝血的作用，即更具生理相关性的凝血臂，尚未得到研究。我们假设 C1q 与 gC1qR 的结合增强了外膜成纤维细胞和血管平滑肌细胞中组织因子（TF）的表达，这些细胞是体内主要的 TF 载体细胞。
方法
使用酶联免疫吸附测定方法，观察 TF 表达和 gC1qR 的作用。将细胞用 C1q 或 gC1qR 阻断剂孵育 1 小时，以评估 gC1qR 的作用。此外，监测细胞生长特征以评估活力和代谢活性的变化。
结果
我们的结果表明，与未处理的细胞相比，孵育 C1q 后 TF 的表达显著增加。与单独用阻断抗体处理的细胞相比，用 gC1qR 阻断剂和 C1q 处理的细胞中 TF 表达没有变化。在这些条件下，代谢活性或细胞活力没有显著差异。
结论
这表明 gC1qR 与 C1q 的结合诱导 TF 表达并可能引发外源性凝血。总的来说，这些数据表明 C1q 在激活外源性凝血中的作用，并且 gC1qR 活性可能将炎症和血栓形成联系起来。
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