title: Extracellular signal-regulated kinase 1/2-mediated phosphorylation of cytosolic phospholipase A2 is essential for human eosinophil adhesion to fibronectin.
abstract: We examined the role of p38, p42, and p44 mitogen-activated protein kinase (MAPK) isoforms and cytosolic phospholipase A(2) (cPLA(2)) activation in human eosinophil adhesion to plate-coated fibronectin (FN). In the control state, eosinophil adhesion was maximal, with 10 microg/ml FN at 30 min, and decreased after 60-90 min. Western blot analysis demonstrated that p44/42 MAPK (extracellular signal-regulated kinase (ERK)1/2) and cPLA(2) were phosphorylated during adhesion to FN, whereas p38 MAPK phosphorylation was unchanged. Preincubation of eosinophils with U0126 or PD98059, two structurally unrelated MAPK kinase inhibitors, or arachidonic trifluoromethyl ketone, a cPLA(2) inhibitor, blocked eosinophil adhesion to FN. By contrast, eosinophil adhesion was unaffected by SB203580, a p38 MAPK inhibitor. Pretreatment of eosinophils with okadaic acid, a serine/threonine phosphatase inhibitor, at the concentrations that induced ERK1/2 and cPLA(2) phosphorylation caused an increase in maximal eosinophil adhesion to FN for >60 min. MAPK kinase inhibition but not p38 inhibition also blocked FN-mediated F-actin redistribution in eosinophils and prevented cPLA(2) phosphorylation caused by adhesion to FN. These results demonstrate that ERK1/2 mediating cPLA(2) activation is essential for eosinophil adhesion to FN.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sano
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: A
authors.initials: A
authors.lastname: Sano
authors.forename: E E
authors.initials: EE
authors.lastname: Boetticher
authors.forename: T
authors.initials: T
authors.lastname: Shioya
authors.forename: B
authors.initials: B
authors.lastname: Jacobs
authors.forename: N M
authors.initials: NM
authors.lastname: Munoz
authors.forename: A R
authors.initials: AR
authors.lastname: Leff
mesh_terms: D000199:Actins / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D048728:MAP Kinase Kinase Kinase 1; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D054467:Phospholipases A2; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000199:Actins; D002070:Butadienes; D004791:Enzyme Inhibitors; D005353:Fibronectins; D007527:Isoenzymes; D009570:Nitriles; C113580:U 0126; D019319:Okadaic Acid; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D010741:Phospholipases A; D054467:Phospholipases A2