Urokinase induces basophil chemotaxis through a urokinase receptor epitope that is an endogenous ligand for formyl peptide receptor-like 1 and -like 2.

Abstract. Basophils circulate in the blood and are able to migrate into tissues at the sites of inflammation. Urokinase plasminogen activator (uPA) binds a specific high affinity surface receptor (uPAR). The uPA-uPAR system is crucial for cell adhesion and migration, and tissue repair. We have investigated the presence and function of the uPA-uPAR system in human basophils. uPAR expression was found at both mRNA and protein level. The receptor was expressed on the cell surface of basophils, in the intact and cleaved forms. Basophils did not express uPA either at protein or mRNA level. uPA (10-12 – 10-9 M) and its uPAR-binding aminoterminal fragment (ATF) were potent chemoattractants for basophils, but did not induce histamine or cytokine release. Inactivation of uPA enzymatic activity by DFP did not affect its chemotactic activity. A polyclonal antibody against uPAR inhibited uPA-dependent basophil chemotaxis. The uPAR-derived peptide 84-95 (uPAR84-95) induced basophil chemotaxis. Basophils expressed mRNA for the formyl peptide receptors FPR, FPRL1 and FPRL2. The FPR antagonist cyclosporin H prevented chemotaxis induced by FMLP, but not by uPA and uPAR84-95. Incubation of basophils with low and high concentrations of FMLP, which desensitize FPR and FPRL1, respectively, but not FPRL2, slightly reduced the chemotactic response to uPA and uPAR84-95. In contrast, desensitization with WKYMVm, which binds also FPRL2, markedly inhibited the response to both molecules. Thus, uPA is a potent chemoattractant for basophils, which seems to act through exposure of the chemotactic uPAR epitope uPAR84-95, which is an endogenous ligand for FPRL2 and FPRL1.