Current View on the Molecular Mechanisms Underlying Fibrin(ogen)-Dependent Inflammation.
Current View on the Molecular Mechanisms Underlying Fibrin(ogen)-Dependent Inflammation.
复制标题
DOI：
10.1055/a-1910-4538
复制
发表时间：
2022-11
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
许多研究表明纤维蛋白原参与炎症反应。为了解释纤维蛋白原依赖性炎症的分子机制，已经提出了两种桥接机制，其中纤维蛋白（原）将白细胞桥接到内皮细胞。第一种机制表明，桥接通过纤维蛋白原与白细胞受体Mac-1和内皮受体ICAM-1的相互作用发生，其促进白细胞迁移并增强炎症。第二种机制包括纤维蛋白降解产物E1片段通过与白细胞受体CD 11 c和内皮细胞VE-钙粘蛋白相互作用，促进白细胞向内皮细胞的桥接，从而促进白细胞的迁移。纤维蛋白衍生的β15-42片段抑制了E1在促进炎症中的作用，这被认为是由于其竞争E1-VE-钙粘蛋白相互作用并通过Src激酶Fyn触发信号通路的能力。我们最近的研究表明，β15-42片段在抑制E1-或纤维蛋白-VE-钙粘蛋白相互作用方面是无效的，使得所提出的信号传导机制成为β15-42抑制功能的唯一可行解释。我们已经发现，纤维蛋白与VLDL受体相互作用，这种相互作用触发了一个信号通路，通过抑制src激酶Fyn促进白细胞迁移。该途径被β15-42与假定的内皮受体相互作用诱导的另一途径抑制。本文简要介绍了纤维蛋白依赖性炎症的分子机制及其优缺点，并对近年来在纤维蛋白依赖性炎症中起重要作用的VLDL受体依赖性白细胞迁移途径的研究进展进行了综述。
Numerous studies have revealed the involvement of fibrinogen in the inflammatory response. To explain the molecular mechanisms underlying fibrinogen-dependent inflammation, two bridging mechanisms have been proposed in which fibrin(ogen) bridges leukocytes to endothelial cells. The first mechanism suggests that bridging occurs via the interaction of fibrinogen with the leukocyte receptor Mac-1 and the endothelial receptor ICAM-1, which promotes leukocyte transmigration and enhances inflammation. The second mechanism includes bridging of leukocytes to the endothelium by fibrin degradation product E1 fragment through its interaction with leukocyte receptor CD11c and endothelial VE-cadherin to promote leukocyte transmigration. The role of E1 in promoting inflammation is inhibited by the fibrin-derived β15-42 fragment, and this has been suggested to result from its ability to compete for the E1-VE-cadherin interaction and to trigger signaling pathways through the Src kinase Fyn. Our recent study revealed that the β15-42 fragment is ineffective in inhibiting the E1- or fibrin-VE-cadherin interaction, leaving the proposed signaling mechanism as the only viable explanation for the inhibitory function of β15-42. We have discovered that fibrin interacts with the VLDL receptor, and this interaction triggers a signaling pathway that promotes leukocyte transmigration through inhibition of src kinase Fyn. This pathway is inhibited by another pathway induced by the interaction of β15-42 with a putative endothelial receptor. In this review, we briefly describe the previously proposed molecular mechanisms underlying fibrin-dependent inflammation and their advantages/disadvantages and summarize our recent studies of the novel VLDL receptor-dependent pathway of leukocyte transmigration which plays an important role in fibrin-dependent inflammation.
登录
查看更多内容
影响因子：
3.7
作者：
Gröger M;Pasteiner W;Ignatyev G;Matt U;Knapp S;Atrasheuskaya A;Bukin E;Friedl P;Zinkl D;Hofer-Warbinek R;Zacharowski K;Petzelbauer P;Reingruber S
通讯作者：
Reingruber S
影响因子：
27.4
作者：
BARNHART, MI;RIDDLE, JM;BLUHM, GB
通讯作者：
BLUHM, GB
影响因子：
4.8
作者：
Holinstat, M;Knezevic, N;Mehta, D
通讯作者：
Mehta, D
影响因子：
16
作者：
Fisher, C;Beglova, N;Blacklow, SC
通讯作者：
Blacklow, SC
影响因子：
30.5
作者：
Akassoglou, Katerina
通讯作者：
Akassoglou, Katerina