Malik A B, Lo S K, Bizios R
Ann N Y Acad Sci. 1986;485:293-309. doi: 10.1111/j.1749-6632.1986.tb34591.x.
Figure 15 summarizes the current understanding of mechanisms of endothelial permeability alterations induced with thrombin. If thrombin generation exceeds the antiprotease activity, thrombin results in clotting of fibrinogen and intravascular fibrin accumulation. Pulmonary neutrophil sequestration also occurs after fibrin deposition, and this is related to the degree and duration of fibrin sequestration. Neutrophil activation appears to be an essential requirement for the mediation of the pulmonary vascular injury. Thrombin-induced intravascular coagulation results in the generation of lipid mediators (LTB4 and HETEs), which may be involved in increasing endothelial permeability. The release of thrombin in higher concentrations during lysis of fibrin (sequence; see text) FIGURE 15. Hypothesis showing mechanisms of thrombin-induced increase in endothelial permeability to proteins. Thrombin may have direct effects on endothelial permeability, or thrombin induced fibrinogen clotting, activation of neutrophils, and the release of lipid metabolites that subsequently lead to an increase in endothelial permeability. clots may induce a direct formation of interendothelial "gaps." Therefore, the vascular injury induced by neutrophil activation and the formation of endothelial "gaps" induced directly by thrombin can both increase the endothelial permeability to proteins. Thrombin is an important mediator of increased endothelial permeability to macromolecules, and may participate in the inflammatory response. In this regard, thrombin may be similar to other mediators (such as histamine and serotonin) that have been previously documented to increase macromolecule transport across the endothelium. The implications of free thrombin in increasing endothelial permeability may be greater because thrombin not only has a direct effect on endothelial permeability, but also induces clotting of fibrinogen and the subsequent generation of mediators that activate neutrophils and that in turn can induce endothelial injury.
图15总结了目前对凝血酶诱导内皮通透性改变机制的理解。如果凝血酶生成超过抗蛋白酶活性，凝血酶会导致纤维蛋白原凝结和血管内纤维蛋白积聚。纤维蛋白沉积后也会发生肺中性粒细胞滞留，这与纤维蛋白滞留的程度和持续时间有关。中性粒细胞活化似乎是介导肺血管损伤的必要条件。凝血酶诱导的血管内凝血会产生脂质介质（白三烯B4和羟二十碳四烯酸），它们可能参与增加内皮通透性。在纤维蛋白溶解过程中更高浓度凝血酶的释放（顺序；见正文）图15。显示凝血酶诱导内皮对蛋白质通透性增加机制的假说。凝血酶可能对内皮通透性有直接影响，或者凝血酶诱导纤维蛋白原凝结、中性粒细胞活化以及脂质代谢产物的释放，随后导致内皮通透性增加。凝块可能诱导内皮间“间隙”的直接形成。因此，中性粒细胞活化诱导的血管损伤和凝血酶直接诱导的内皮“间隙”形成都可增加内皮对蛋白质的通透性。凝血酶是内皮对大分子通透性增加的重要介质，可能参与炎症反应。在这方面，凝血酶可能类似于先前已证明可增加大分子跨内皮转运的其他介质（如组胺和5-羟色胺）。游离凝血酶在增加内皮通透性方面的影响可能更大，因为凝血酶不仅对内皮通透性有直接作用，还诱导纤维蛋白原凝结以及随后激活中性粒细胞并进而可诱导内皮损伤的介质的产生。
