CXCR3 expression and activation of eosinophils: role of IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma.
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.
Jinquan
T
T
Laboratory of Medical Allergology, Allergy Unit, National University Hospital, University of Copenhagen, Copenhagen, Denmark. tan@rh.dk
Jing
C
C
Jacobi
H H
HH
Reimert
C M
CM
Millner
A
A
Quan
S
S
Hansen
J B
JB
Dissing
S
S
Malling
H J
HJ
Skov
P S
PS
Poulsen
L K
LK
D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000378:metabolism / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism; D008024:Ligands; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000502:physiology; D018121:Receptors, Cytokine / Q000502:physiology; D012260:Ribonucleases; D015398:Signal Transduction / Q000276:immunology
D001798:Blood Proteins; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D047091:Eosinophil Granule Proteins; C104577:IP10-Mig receptor; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D007376:Interleukin-2; D008024:Ligands; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D016753:Interleukin-10; D007371:Interferon-gamma; D012260:Ribonucleases; D002118:Calcium