TY - JOUR

T1 - CXCR3 expression and activation of eosinophils

T2 - role of IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma

AU - Jinquan, T

AU - Jing, C

AU - Jacobi, H H

AU - Reimert, C M

AU - Millner, A

AU - Quan, S

AU - Hansen, J B

AU - Dissing, S

AU - Malling, H J

AU - Skov, P S

AU - Poulsen, L K

PY - 2000/8/1

Y1 - 2000/8/1

N2 - CXC chemokine receptor 3 (CXCR3), predominately expressed on memory/activated T lymphocytes, is a receptor for both IFN-gamma-inducible protein-10 (gamma IP-10) and monokine induced by IFN-gamma (Mig). We report a novel finding that CXCR3 is also expressed on eosinophils. gamma IP-10 and Mig induce eosinophil chemotaxis via CXCR3, as documented by the fact that anti-CXCR3 mAb blocks gamma IP-10- and Mig-induced eosinophil chemotaxis. gamma 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. gamma IP-10 and Mig act eosinophils to induce chemotaxis via the cAMP-dependent protein kinase A signaling pathways. The fact that gamma IP-10 and Mig induce an increase in intracellular calcium in eosinophils confirms that CXCR3 exists on eosinophils. Besides induction to chemotaxis, gamma IP-10 and Mig also activate eosinophils to eosinophil cationic protein release. These results indicate that CXCR3-gamma 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.

AB - CXC chemokine receptor 3 (CXCR3), predominately expressed on memory/activated T lymphocytes, is a receptor for both IFN-gamma-inducible protein-10 (gamma IP-10) and monokine induced by IFN-gamma (Mig). We report a novel finding that CXCR3 is also expressed on eosinophils. gamma IP-10 and Mig induce eosinophil chemotaxis via CXCR3, as documented by the fact that anti-CXCR3 mAb blocks gamma IP-10- and Mig-induced eosinophil chemotaxis. gamma 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. gamma IP-10 and Mig act eosinophils to induce chemotaxis via the cAMP-dependent protein kinase A signaling pathways. The fact that gamma IP-10 and Mig induce an increase in intracellular calcium in eosinophils confirms that CXCR3 exists on eosinophils. Besides induction to chemotaxis, gamma IP-10 and Mig also activate eosinophils to eosinophil cationic protein release. These results indicate that CXCR3-gamma 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.

KW - Blood Proteins

KW - Calcium

KW - Chemokine CXCL10

KW - Chemokine CXCL9

KW - Chemokines, CXC

KW - Chemotaxis, Leukocyte

KW - Eosinophil Granule Proteins

KW - Eosinophils

KW - Humans

KW - Inflammation Mediators

KW - Intercellular Signaling Peptides and Proteins

KW - Interferon-gamma

KW - Interleukin-10

KW - Interleukin-2

KW - Intracellular Fluid

KW - Ligands

KW - Receptors, CXCR3

KW - Receptors, Chemokine

KW - Receptors, Cytokine

KW - Ribonucleases

KW - Signal Transduction

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Journal article

C2 - 10903763

VL - 165

SP - 1548

EP - 1556

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -