CXCR3 Expression And Activation Of Eosinophils:Role Of IFN-γ-Inducible Protein-10 And Monokine Induced By IFN-γ

CXCR3, predominately expressed on memory/activated T lymphocytes, is a receptor for both yIP-l0 and Mig. We report a novel finding that CXCR3 is also expressed on eosinophils. yIP-10 and Mig induce eosinophil chemotaxis via CXCR3 documented by the fact that anti-CXCR3 mAb blocks yIP-10 and Mig-induced eosinophil chemotaxis. ylIP-10 and Mig-induced eosinophil chemotaxis are up- and down-regulated by IL-2 and IL-b, respectively. Correspondingly, CXCR3 protein and mRNA expression in eosinophils is up- and down-regulated by IL-2 and IL- 10 detected by using flow cytometry, imrnunocytochemical assay and real time quantitative RT-PCR technique. yIP-10 and Mig act eosinophils to induce chemotaxis via cAMP-dependent protein kinase A signaling pathways. The fact that yIP-10 and Mig induce increase in (Ca2~) i in eosonophils confirms that CXCR3 exists on eosinophils. Besides induction to chemotaxis, yIP-1O and Mig also activate eosinophils to ECP release. Surprisingly, ylP-1O and Mig stimulate activation of NFAT1 and NFAT4 in eosinophils in terms of NFAT complex nuclear translocation. These results indicate that CXCR3- ylP-10 and -Mig receptor-ligand pairs as well as the effects of IL-2 and IL-b on them may be especially important in cytokine/chemokine environment for the pathophysiological events of allergic inflammation including initiation, progression and termination in the processes.