title: Cytosolic phospholipase A2 activation is essential for beta 1 and beta 2 integrin-dependent adhesion of human eosinophils.
abstract: We examined the role of cytosolic phospholipase A2 (cPLA2) during human eosinophil adherence to ICAM-1- or VCAM-1-coated plates. IL-5-stimulated eosinophils adhered to ICAM-1 through the beta 2 integrin CD11b/CD18, while nonstimulated eosinophils did not. By contrast, nonstimulated eosinophils adhered to VCAM-1 through the beta 1-integrin VLA-4/CD29. Both IL-5-induced adhesion to ICAM-1 and spontaneous adhesion to VCAM-1 corresponded temporally to cPLA2 phosphorylation, which accompanied enhanced catalytic activity of cPLA2. The structurally unrelated cPLA2 inhibitors, arachidonyl trifluoromethylketone and surfactin, significantly inhibited eosinophil adhesion to ICAM-1 and VCAM-1 in a concentration-dependent manner. Inhibition of secretory PLA2, 5-lipoxygenase, or cyclooxygenase did not affect eosinophil adhesion. Addition of arachidonic acid to eosinophils after cPLA2 inhibition with arachidonyl trifluoromethylketone or surfactin did not reverse the blockade of adhesion to ICAM-1 or VCAM-1. However, CV-6209, a receptor-specific antagonist of platelet-activating factor, inhibited all integrin-mediated adhesion. The activated conformation of CD11b as identified by the mAb, CBRM1/5, as well as quantitative surface CD11b expression were up-regulated after IL-5 stimulation. However, cPLA2 inhibition neither prevented CBRM1/5 expression nor blocked surface Mac-1 up-regulation caused by IL-5. Our data suggest that cPLA2 activation and its catalytic product platelet-activating factor play an essential role in regulating beta 1 and beta 2 integrin-dependent adhesion of eosinophils. This blockade occurs even in the presence of up-regulated eosinophil surface integrin.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, Division of Biological Sciences, University of Chicago, Illinois 60607, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: N M
authors.initials: NM
authors.lastname: Muñoz
authors.forename: K P
authors.initials: KP
authors.lastname: Kim
authors.forename: H
authors.initials: H
authors.lastname: Sano
authors.forename: W
authors.initials: W
authors.lastname: Cho
authors.forename: A R
authors.initials: AR
authors.lastname: Leff
mesh_terms: D001095:Arachidonic Acids / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology; D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology*; D004789:Enzyme Activation / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000502:physiology*; D000939:Epitopes / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D015848:Interleukin-5 / Q000494:pharmacology; D055666:Lipopeptides; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D010456:Peptides, Cyclic; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D010766:Phosphorylation; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
chemical_list: D001095:Arachidonic Acids; D001426:Bacterial Proteins; D018821:CD18 Antigens; D004791:Enzyme Inhibitors; D000939:Epitopes; D019012:Integrin beta1; D015848:Interleukin-5; D055666:Lipopeptides; D016177:Macrophage-1 Antigen; D010456:Peptides, Cyclic; D019010:Vascular Cell Adhesion Molecule-1; C081565:arachidonyltrifluoromethane; D018799:Intercellular Adhesion Molecule-1; C009365:surfactin peptide; D010741:Phospholipases A; D054467:Phospholipases A2