Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
J Leukoc Biol. 2020 Jul;108(1):93-103. doi: 10.1002/JLB.3MR0120-390R. Epub 2020 Mar 14.
Eosinophils are often cited as playing roles in wound healing and epithelial remodeling; however, the exact triggers and mechanisms of such activity remain poorly understood. Eosinophils show the remarkable capacity to partner with coagulation, which is a highly conserved biologic system evolved to protect an organism from injury by promoting hemostasis and tissue repair. Eosinophils contribute directly by producing key factors in coagulation (tissue factor, thrombin) and fibrinolysis (plasminogen). Moreover, they have been shown to interact with other players in these cascades, such as fibrinogen and the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system, which further promotes coagulation and fibrinolysis. Although primarily thought of in the contexts of blood clotting and vascular repair, coagulation and fibrinolytic systems play key roles within tissue, in particular during epithelial injury and remodeling. Chronic inflammation and remodeling frequently associate with pro-thrombotic and pro-coagulation state. There is a striking association between eosinophils and dysregulated coagulation in animal models and human disease. This review will examine the mechanistic links between eosinophils and the coagulation system in the context of epithelial injury and repair, as well as evidence for this interaction in heart disease, type 2 inflammatory diseases, and cancer. Collectively, multiple emerging studies summarized in this review elucidate an overlooked, but potentially fundamental, biologic mechanism to engage eosinophils in processes of epithelial injury and repair.
嗜酸性粒细胞常被认为在伤口愈合和上皮重塑中发挥作用；然而，这种活动的确切触发因素和机制仍知之甚少。嗜酸性粒细胞具有与凝血作用密切相关的显著能力，凝血作用是一种高度保守的生物系统，其进化目的是通过促进止血和组织修复来保护生物体免受伤害。嗜酸性粒细胞通过产生凝血（组织因子、凝血酶）和纤维蛋白溶解（纤溶酶原）中的关键因子直接发挥作用。此外，已经表明它们可以与这些级联反应中的其他参与者相互作用，例如纤维蛋白原和尿激酶型纤溶酶原激活物/尿激酶型纤溶酶原激活物受体系统，这进一步促进了凝血和纤维蛋白溶解。尽管凝血和纤维蛋白溶解系统主要被认为是在血液凝固和血管修复的背景下发挥作用，但它们在组织中，特别是在上皮损伤和重塑过程中，起着关键作用。慢性炎症和重塑经常与促血栓形成和促凝状态相关。在动物模型和人类疾病中，嗜酸性粒细胞与失调的凝血之间存在惊人的关联。本综述将探讨嗜酸性粒细胞与凝血系统在上皮损伤和修复中的机制联系，以及在心脏病、2 型炎症性疾病和癌症中这种相互作用的证据。总之，本综述中总结的多项新兴研究阐明了一种被忽视但潜在的基本生物学机制，即通过嗜酸性粒细胞参与上皮损伤和修复过程。
