Eosinophils in wound healing and epithelial remodeling: Is coagulation a missing link?

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.