Blockade of JAK2 by tyrphostin AG-490 inhibits antigen-induced eosinophil recruitment into the mouse airways.
We studied the effect of tyrphostin AG-490, a specific Janus kinase 2 (JAK2) inhibitor, on antigen-induced eosinophil recruitment into the airways of sensitized mice and on IL-5-induced chemokinesis and adhesiveness of eosinophils. The in vivo administration of AG-490 prevented antigen-induced eosinophil infiltration in the airways of sensitized mice in a dose-dependent manner. However, the administration of AG-490 did not affect antigen-induced IL-5 production in the airways nor in vitro antigen-induced IL-5 production and T cell proliferation of spleen cells. Furthermore, AG-490 inhibited IL-5-induced chemokinesis and beta1-integrin adhesiveness of eosinophils in vitro. Because antigen-induced eosinophil recruitment into the airways is mediated by IL-5, these results indicate that JAK2 activation is critical for antigen-induced, IL-5-dependent mobilization of eosinophils into the tissue.
Kumano
K
K
Department of Medicine II, Chiba University School of Medicine, Chiba, Japan.
Nakao
A
A
Nakajima
H
H
Miike
S
S
Kurasawa
K
K
Saito
Y
Y
Iwamoto
I
I
D000818:Animals; D018926:Anti-Allergic Agents / Q000378:metabolism; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D015848:Interleukin-5 / Q000032:analysis; D053614:Janus Kinase 2; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D039041:Integrin alpha4beta1; D016023:Integrins; D015848:Interleukin-5; D011518:Proto-Oncogene Proteins; D016201:Receptors, Lymphocyte Homing; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D010047:Ovalbumin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2