REGULATION OF LEUKOCYTE-ENDOTHELIUM INTERACTION AND LEUKOCYTE TRANSENDOTHELIAL MIGRATION BY INTERCELLULAR-ADHESION MOLECULE 1-FIBRINOGEN RECOGNITION
REGULATION OF LEUKOCYTE-ENDOTHELIUM INTERACTION AND LEUKOCYTE TRANSENDOTHELIAL MIGRATION BY INTERCELLULAR-ADHESION MOLECULE 1-FIBRINOGEN RECOGNITION
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DOI：
10.1073/pnas.92.5.1505
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发表时间：
1995-02-28
影响因子：
11.1
通讯作者：
ALTIERI, DC
中科院分区：
文献类型：
--
作者：
LANGUINO, LR;DUPERRAY, A;ALTIERI, DC
虽然纤维蛋白原主要因其在止血中的作用而被认可，但纤维蛋白原对于体内有效的炎症反应也是必需的。现在表明，纤维蛋白原促进终末分化的骨髓单核细胞的内皮单层的粘附和迁移，该过程不需要内皮的趋化/趋触梯度或细胞因子刺激，并且对于纤维蛋白原与细胞间粘附分子1（ICAM-1）的结合具有特异性。在其他粘附性血浆蛋白中，纤连蛋白不能增加白细胞与内皮的结合或跨内皮迁移，而玻连蛋白促进结合但不促进迁移。纤维蛋白原介导的白细胞粘附和跨内皮迁移可以被来自纤维蛋白原伽马链序列 N(117)NQKIVNLKEKVAQLEA(133) 的肽抑制，该肽阻断内皮细胞的结合纤维蛋白原转化为 ICAM-1。这种相互作用也可以被不影响 ICAM-1-CD11a/CD18 识别的新型抗 ICAM-1 单克隆抗体抑制，因此表明 ICAM-1 上的纤维蛋白原结合位点在结构上可能与先前涉及白细胞-内皮相互作用的区域不同。因此，纤维蛋白原与血管细胞受体的结合足以启动（i）增加白细胞与内皮的粘附和（ii）白细胞跨内皮迁移，这两个过程是免疫炎症反应的最早事件，也可能导致动脉粥样硬化。
Although primarily recognized for its role in hemostasis, fibrinogen is also required for competent inflammatory reactions in vivo, It is now shown that fibrinogen promotes adhesion to and migration across an endothelial monolayer of terminally differentiated myelomonocytic cells, This process does not require chemotactic/haptotactic gradients or cytokine stimulation of the endothelium and is specific for the association of fibrinogen with intercellular adhesion molecule 1 (ICAM-1) on endothelium, Among other adhesive plasma proteins, fibronectin fails to increase the binding of leukocytes to endothelium, or transendothelial migration, whereas vitronectin promotes the binding but not the migration, The fibrinogen-mediated leukocyte adhesion and transendothelial migration could be inhibited by a peptide from the fibrinogen gamma-chain sequence N(117)NQKIVNLKEKVAQLEA(133), which blocks the binding of fibrinogen to ICAM-1. This interaction could also be inhibited by new anti-ICAM-1 monoclonal antibodies that did not affect the ICAM-1-CD11a/CD18 recognition, thus suggesting that the fibrinogen binding site on ICAM-1 may be structurally distinct from regions previously implicated in leukocyte-endothelium interaction, Therefore, binding of fibrinogen to vascular cell receptors is sufficient to initiate (i) increased leukocyte adhesion to endothelium and (ii) leukocyte transendothelial migration, These two processes are the earliest events of immune inflammatory responses and may also contribute to atherosclerosis.