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-B-induced chemokinesis and adhesive ness of eosin ophils. The in vivo administration of AG-490 prevented antigen-induced eosi nophil infiltration in the airways of sensitized mice in a dose-dependent m anner. However, the administration of AG-490 did not affect antigen-induced IL-5 production in the airways nor in vitro antigen-induced IL-5 productio n and T cell proliferation of spleen cells. Furthermore, AG-490 inhibited I L-B-induced chemokinesis and beta 1-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 f or antigen-induced, IL-5-dependent mobilization of eosinophils into the tis sue. (C) 2000 Academic Press.