Signalling pathways regulating human neutrophil migration induced by secretory phospholipases A(2)

dc.creatorGambero, A
dc.creatorThomazzi, SM
dc.creatorCintra, ACO
dc.creatorLanducci, ECT
dc.creatorDe Nucci, G
dc.creatorAntunes, E
dc.date2004
dc.dateOCT
dc.date2014-11-15T15:02:53Z
dc.date2015-11-26T17:20:27Z
dc.date2014-11-15T15:02:53Z
dc.date2015-11-26T17:20:27Z
dc.date.accessioned2018-03-29T00:08:03Z
dc.date.available2018-03-29T00:08:03Z
dc.identifierToxicon. Pergamon-elsevier Science Ltd, v. 44, n. 5, n. 473, n. 481, 2004.
dc.identifier0041-0101
dc.identifierWOS:000224671700002
dc.identifier10.1016/j.toxicon.2004.06.004
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/75566
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/75566
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/75566
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1283140
dc.descriptionThis study was designed to elucidate the signalling pathways by which secretory phospholipases A(2) (sPLA(2)s) induce in vitro neutrophil migration. The cell migration assays were performed with Naja mocambique venom PLA(2) (sPLA(2) with high catalytic activity), bothropstoxin-I (sPLA2 devoid of catalytic activity) and platelet-activating factor (PAF), using a 48-well microchemotaxis chamber. Both the non-selective protein kinase inhibitor staurosporine (30-300 nM) and the selective protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpyperazine (H7; 50-200 muM) as well as the Gi inactivator pertussis toxin (30-300 nM) caused a concentration-dependent inhibition of the neutrophil migration induced by either N. mocambique venom PLA(2) (100 mug/ml) or bothropstoxin-I (100 mug/ml). Pertussis toxin nearly abolished PAF-induced migration, while staurosporine and H7 partly (but significantly) inhibited the chemotactic responses to PAR The dual inhibitor of cytosolic PLA(2) and Ca2+-independent PLA(2) (iPLA(2)), arachidonil-trifluoromethyl-ketone (ATK; 0.2-20 muM), or the specific iPLA(2) inhibitor bromoenol lactone (1-30 muM) caused a concentration-dependent inhibition of the migration induced by either sPLA(2)s. At the maximal concentration used for each compound, the migration was almost suppressed. In contrast, both of these compounds caused only slight inhibitions of PAF-induced migration. No rise in intracellular Ca2+ Was observed in neutrophil-stimulated sPLA(2), as determined in cells preloaded with fura 2-AM. In the experimental condition used, pertussis toxin, staurosporine, H7, ATK or bromoenol lactone did not induce cytotoxic effects, according to MTT assay. Our results suggest that activation of an endogenous PLA(2) through activation of GTP-binding protein and PKC is the main mechanism by which exogenous sPLA(2)s cause neutrophil migration. (C) 2004 Elsevier Ltd. All rights reserved.
dc.description44
dc.description5
dc.description473
dc.description481
dc.languageen
dc.publisherPergamon-elsevier Science Ltd
dc.publisherOxford
dc.publisherInglaterra
dc.relationToxicon
dc.relationToxicon
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectphospholipase A(2)
dc.subjectneutrophil migration
dc.subjectG-protein
dc.subjectprotein kinase C
dc.subjectintracellular Ca2+
dc.subjectHuman Polymorphonuclear Leukocytes
dc.subjectAmino-acid-sequence
dc.subjectProtein-kinase-c
dc.subjectArachidonic-acid
dc.subjectPertussis Toxin
dc.subjectTrifluoromethyl Ketone
dc.subjectChemotactic Factor
dc.subjectCalcium-entry
dc.subjectSnake-venom
dc.subjectInhibition
dc.titleSignalling pathways regulating human neutrophil migration induced by secretory phospholipases A(2)
dc.typeArtículos de revistas


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