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(Journal of Leukocyte Biology. 2002;72:1046-1053.)
© 2002 by Society for Leukocyte Biology

IL-5-induced integrin adhesion of human eosinophils caused by ERK1/2-mediated activation of cPLA₂

Xiangdong Zhu^*, Benjamin Jacobs^*, Evan Boetticher^*, Shigeharu Myou^*, Angelo Meliton^*, Hiroyuki Sano, Anissa T. Lambertino^*, Nilda M. Muñoz^* and Alan R. Leff^*

^* Section of Pulmonary and Critical Care Medicine, Department of Medicine and Department of Neurobiology, Pharmacology and Physiology, Pediatrics, Anesthesia and Critical Care, and Committees on Clinical Pharmacology, Cell Physiology and Molecular Medicine, Division of the Biological Sciences, The University of Chicago, Illinois; and
Third Department of Internal Medicine, Tottori University, Japan

Correspondence: Dr. Alan R. Leff, Section of Pulmonary and Critical Care Medicine, Department of Medicine, MC6076, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637. E-mail: aleff{at}medicine.bsd.uchicago.edu

We examined the mechanism by which interleukin (IL)-5 causes ß₂-integrin adhesion of human eosinophils. IL-5 caused time-dependent activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 in eosinophils as detected by their phosphorylation. Preincubation of eosinophils with U0126, a mitogen-activated protein kinase/ERK kinase inhibitor, suppressed IL-5-induced activation of cytosolic phospholipase A₂ (cPLA₂) and eosinophil adhesion, and p38 inhibition by SB203580 had neither effect. ERK1/2 phosphorylation and eosinophil adhesion were blocked by inhibition of the src-family tyrosine kinase, Janus tyrosine kinase (JAK)2, or phosphoinositide-3 kinase (PI3K). Coimmunoprecipitation assay demonstrated that Lyn, a src-family tyrosine kinase, was constitutively associated with PI3K. Inhibition of src-tyrosine kinase but not JAK2 suppressed PI3K activation. Our data suggest that IL-5 induces ß₂-integrin adhesion of human eosinophils by regulation of cPLA₂ activation caused by ERK1/2 phosphorylation. This phosphorylation results from activation of PI3K and protein tyrosine kinases. We also find that src-family tyrosine kinase, possibly Lyn, is the upstream kinase causing PI3K activation.

Key Words: adhesion molecules • signal transduction • arachidonic acid

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