Background: Protease-activated receptors (PARs) are a unique class of G-protein-coupled receptors, which are activated by proteolytic cleavage of the amino terminus of the receptor itself. Although expression of the PAR1, which is typically activated by thrombin, on human eosinophils has been demonstrated, no effect of thrombin on eosinophil function has been shown yet. Thus we investigated whether thrombin affects eosinophil migration in vitro. Methods: Eosinophils were obtained from venous blood of healthy donors. Cell migration was studied by micropore filter assays. Involvement of PARs in thrombin-dependent migration was tested functionally using selective agonist peptides for PARs and a cleavage blocking PAR1 antibody. Results: Thrombin significantly stimulated eosinophil chemotaxis in a dose-dependent manner. This effect was mimicked by the PAR1 but not the PAR2 agonist and was reversed by the cleavage blocking PAR1 antibody. Checkerboard experiments indicated that eosinophil migration depends on the presence of thrombin in a concentration gradient. Conclusions: Data suggest that activation of PAR1 by thrombin stimulates directed migration of human eosinophils and thereby may affect eosinophils in tissue and allergic inflammation.

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