Transcellular secretion of group V phospholipase A2 from epithelium induces beta 2-integrin-mediated adhesion and synthesis of leukotriene C4 in eosinophils
| Autor: | Anissa Lambertino, Nilda M. Munoz, Alan R. Leff, Angelo Y. Meliton, Faraz Sultan, Evan Boetticher, Xiangdong Zhu, Jonathan Learoyd, Wonhwa Cho |
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| Rok vydání: | 2006 |
| Předmět: |
Immunology
Integrin Biology Phospholipases A Cell Line Group V Phospholipases A2 chemistry.chemical_compound Phospholipase A2 Cytosol Cell Adhesion Immunology and Allergy Humans Phosphorylation Cytochalasin B Mitogen-Activated Protein Kinase 1 Leukotriene Phospholipase A Arachidonic Acid Mitogen-Activated Protein Kinase 3 Leukotriene C4 Lysophosphatidylcholines Epithelial Cells Cell biology Eosinophils Isoenzymes N-Formylmethionine Leucyl-Phenylalanine Phospholipases A2 Protein Transport chemistry Integrin alpha M CD18 Antigens biology.protein Arachidonic acid |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 177(1) |
| ISSN: | 0022-1767 |
| Popis: | We examined the mechanism by which secretory group V phospholipase A(2) (gVPLA(2)) secreted from stimulated epithelial cells activates eosinophil adhesion to ICAM-1 surrogate protein and secretion of leukotriene (LT)C(4). Exogenous human group V PLA(2) (hVPLA(2)) caused an increase in surface CD11b expression and focal clustering of this integrin, which corresponded to increased beta(2) integrin-mediated adhesion. Human IIaPLA(2), a close homolog of hVPLA(2), or W31A, an inactive mutant of hVPLA(2), did not affect these responses. Exogenous lysophosphatidylcholine but not arachidonic acid mimicked the beta(2) integrin-mediated adhesion caused by hVPLA(2) activation. Inhibition of hVPLA(2) with MCL-3G1, a mAb against gVPLA(2), or with LY311727, a global secretory phospholipase A(2) (PLA(2)) inhibitor, attenuated the activity of hVPLA(2); trifluoromethylketone, an inhibitor of cytosolic group IVA PLA(2) (gIVA-PLA(2)), had no inhibitory effect on hVPLA(2)-mediated adhesion. Activation of beta(2) integrin-dependent adhesion by hVPLA(2) did not cause ERK1/2 activation and was independent of gIVA-PLA(2) phosphorylation. In other studies, eosinophils cocultured with epithelial cells were stimulated with FMLP/cytochalasin B (FMLP/B) and/or endothelin-1 (ET-1) before LTC(4) assay. FMLP/B alone caused release of LTC(4) from eosinophils, which was augmented by coculture with epithelial cells activated with ET-1. Addition of MCL-3G1 to cocultured cells caused approximately 50% inhibition of LTC(4) secretion elicited by ET-1, which was blocked further by trifluoromethylketone. Our data indicate that hVPLA(2) causes focal clustering of CD11b and beta(2) integrin adhesion by a novel mechanism that is independent of arachidonic acid synthesis and gIVA-PLA(2) activation. We also demonstrate that gVPLA(2), endogenously secreted from activated epithelial cells, promotes secretion of LTC(4) in cocultured eosinophils. |
| Databáze: | OpenAIRE |
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