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-Inducible Protein-10 and Monokine Induced by IFN-1
*
Laboratory of Medical Allergology, Allergy Unit, National University Hospital, and
Department of Medical Physiology, University of Copenhagen, Copenhagen, Denmark; and
Department of Immunology, Anhui Medical University, Hefei, People’s Republic of China
CXC chemokine receptor 3 (CXCR3), predominately expressed on
memory/activated T lymphocytes, is a receptor for both
IFN-
-inducible protein-10 ( IP-10) and monokine induced by
IFN- (Mig). We report a novel finding that CXCR3 is also expressed
on eosinophils. IP-10 and Mig induce eosinophil chemotaxis via
CXCR3, as documented by the fact that anti-CXCR3 mAb blocks
IP-10- and Mig-induced eosinophil chemotaxis. IP-10- and
Mig-induced eosinophil chemotaxis are up- and down-regulated by IL-2
and IL-10, respectively. Correspondingly, CXCR3 protein and mRNA
expressions in eosinophils are up- and down-regulated by IL-2 and
IL-10, respectively, as detected using flow cytometry,
immunocytochemical assay, and a real-time quantitative RT-PCR
technique. IP-10 and Mig act eosinophils to induce chemotaxis via
the cAMP-dependent protein kinase A signaling pathways. The fact that
IP-10 and Mig induce an increase in intracellular calcium in
eosinophils confirms that CXCR3 exists on eosinophils. Besides
induction to chemotaxis, IP-10 and Mig also activate eosinophils to
eosinophil cationic protein release. These results indicate that
CXCR3- IP-10 and -Mig receptor-ligand pairs as well as the effects
of IL-2 and IL-10 on them may be especially important in the
cytokine/chemokine environment for the pathophysiologic events of
allergic inflammation, including initiation, progression, and
termination in the processes.
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