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

Abstract

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.

The Effect of a Triple Combination of Bevacizumab, Sodium Hyaluronate and a Collagen Matrix Implant in a Trabeculectomy Animal Model

“…Additionally, antibody formation by lymphocytes has been shown to significantly increase fibroblast proliferation and decrease apoptosis in the wound bed and edges [ 32 ]. Recently, eosinophils have been described as important regulators of local immunity and remodeling/repair in both health and disease, showing that eosinophils can downregulate inflammation and repair damaged tissue as well [ 33 ]. The study of the responses of this type of cells is therefore relevant in order to understand the effects of modulating agents on basic cellular biology in the wound healing process.…”

Systems vaccinology analysis of a recombinant vaccinia-based vector reveals diverse innate immune signatures at the injection site

“…Adjuvant signatures were driven by TLRs, cytoplasmic RNA and DNA sensors and the inflammasome, with neutrophils potentially also contributing (Stephen et al ., 2017). By day 7 vaccine transcripts and neutrophils were largely absent, and inflammation was abating, with the presence of what appeared to be tissue repair-associated eosinophils (Coden et al ., 2020; Heredia et al ., 2013; Lloyd et al ., 2018; Toor, 2019; Weller et al ., 2017). Although a previous live-attenuated CHIKV vaccine was associated with some arthropathy (Edelman et al ., 2000), no compelling arthritic signature was evident after SCV vaccination.…”

“…Eosinophils have been reported in pruritic papulovesicular eruptions in a case of generalized vaccinia after smallpox vaccination (Beachkofsky et al ., 2010) and are well described as drivers of allergic diseases such as eosinophilic asthma (Bhalla et al ., 2020; Côté et al ., 2020). However, recently a role for eosinophils in tissue repair and wound healing has emerged (Coden et al ., 2020; Lloyd et al ., 2018), particularly for muscle tissues (Heredia et al ., 2013; Toor, 2019; Weller et al ., 2017). That the eosinophils in these resolving post-vaccination lesions are distinct from inflammatory eosinophils is supported by the absence of IL-5 mRNA expression (S2G Table), with anti-IL-5 therapy used for eosinophilic asthma (Walsh, 2020).…”

High Eosinophil Rates in Patients With Right-to-Left Shunts: An Expected Role, or an Unexpected Risk?

“…Uderhardt et al have demonstrated that eosinophils have the capacity to produce strong endogenous thrombin based on the simultaneous expression of the tissue factor and the provision of a procoagulant phospholipid surface enriched with 12/15-lipoxygenase (12/15-LO) [14,15]. Furthermore, Marx et al have highlighted the role of eosinophils in arterial thrombosis by demonstrating that eosinophil deficiency does not affect the induction time of thrombus formation and arterial occlusion [16].…”