Complement component C1q initiates extrinsic coagulation via the receptor for the globular head of C1q in adventitial fibroblasts and vascular smooth muscle cells.
Complement component C1q initiates extrinsic coagulation via the receptor for the globular head of C1q in adventitial fibroblasts and vascular smooth muscle cells.
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DOI：
10.1002/iid3.769
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发表时间：
2023-01
期刊：
影响因子：
--
通讯作者：
Rubenstein DA
中科院分区：
文献类型：
--
作者：
Freda CT;Yin W;Ghebrehiwet B;Rubenstein DA
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，从而设计出更有效的治疗方法。补体成分1（C1）的激活是先天免疫的关键因素，与循环C1 q的显著浓度相关。当C1 q与gC 1 qR相互作用时，许多病理途径启动。这种相互作用在动脉粥样硬化期间观察到的炎症和内源性凝血的启动中起主要作用。然而，C1的影响和作用的C1 q/gC 1 qR外源性凝血，这是更生理相关的凝血手臂，尚未研究。我们假设C1 q与gC 1 qR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承载细胞。使用酶联免疫吸附试验方法，观察TF表达和gC 1 qR的作用。将细胞用C1 q或gC 1 qR阻断剂和C1 q调节1小时，以评估gC 1 qR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。我们的研究结果表明，TF的表达与C1 q孵育后显着增加相比，未处理的细胞。与单独用阻断抗体调节的细胞相比，用gC 1 qR阻断剂和C1 q调节的细胞在TF表达方面没有变化。我们的研究结果表明，在这些条件下，代谢活性或细胞活力没有显着差异。这表明，gC 1 qR与C1 q的关联诱导TF表达，并可能启动外源性凝血。总的来说，这些数据说明了C1 q在外源性凝血激活中的作用，并且gC 1 qR活性可能与炎症和血栓形成有关。血管疾病与炎症改变和血栓形成有关。我们已经确定了补体活性和外源性凝血激活之间的联系。
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. 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. 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. 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. Vascular diseases are associated with altered inflammation and thrombosis. We have identified a link between complement activity and activation of extrinsic coagulation.
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DOI：
10.4049/jimmunol.0903678
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Amara U;Flierl MA;Rittirsch D;Klos A;Chen H;Acker B;Brückner UB;Nilsson B;Gebhard F;Lambris JD;Huber-Lang M
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影响因子：
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DOI：
10.1016/j.clim.2021.108733
发表时间：
2021-06
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Freda CT;Yin W;Ghebrehiwet B;Rubenstein DA
通讯作者：
Rubenstein DA
影响因子：
5.6
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