title: IL-5-induced integrin adhesion of human eosinophils caused by ERK1/2-mediated activation of cPLA2.
abstract: We examined the mechanism by which interleukin (IL)-5 causes beta(2)-integrin adhesion of human eosinophils. IL-5 caused time-dependent activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38alpha 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 A(2) (cPLA(2)) 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 beta(2)-integrin adhesion of human eosinophils by regulation of cPLA(2) 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.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Chicago, Illinois 60637, USA.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhu
authors.forename: Benjamin
authors.initials: B
authors.lastname: Jacobs
authors.forename: Evan
authors.initials: E
authors.lastname: Boetticher
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Myou
authors.forename: Angelo
authors.initials: A
authors.lastname: Meliton
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sano
authors.forename: Anissa T
authors.initials: AT
authors.lastname: Lambertino
authors.forename: Nilda M
authors.initials: NM
authors.lastname: Muñoz
authors.forename: Alan R
authors.initials: AR
authors.lastname: Leff
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D016023:Integrins / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015848:Interleukin-5 / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010741:Phospholipases A / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D016023:Integrins; D015848:Interleukin-5; D018799:Intercellular Adhesion Molecule-1; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010741:Phospholipases A