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Bromoenol lactone, an inhibitor of Group V1A calcium-independent phospholipase A(2) inhibits antigen-stimulated mast cell exocytosis without blocking Ca2+ influx

Fensome-Green, A; Stannard, N; Li, M; Bolsover, S; Cockcroft, S; (2007) Bromoenol lactone, an inhibitor of Group V1A calcium-independent phospholipase A(2) inhibits antigen-stimulated mast cell exocytosis without blocking Ca2+ influx. CELL CALCIUM , 41 (2) 145 - 153. 10.1016/j.ceca.2006.06.002.

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Abstract

Calcium-independent phospholipase A(2) (iPLA(2)beta) has recently been suggested to regulate Ca2+ entry by activating store-operated Ca2+ channels. These studies have been conducted in mast cells using thapsigargin to deplete intracellular stores. In RBL 2H3 and bone marrow-derived mast cells (BMMCs), Ca2+ entry is critical for exocytosis and therefore we have examined whether the proposed mechanism would be relevant when a physiological stimulus is applied to these cells. Using an iPLA(2)beta antibody, we demonstrate that the 84 kDa iPLA(2)beta is expressed in these mast cells. As bromoenol lactone (BEL) is a suicide-based irreversible inhibitor of iPLA(2)beta it was used to probe this potential mechanism. We observe inhibition of exocytosis stimulated either with antigen or with thapsigargin. However, BEL also inhibits exocytosis when stimulated using a Ca2+ ionophore A23187, which passively transports Ca2+ down a concentration gradient and also in permeabilised mast cells where Ca2+ entry is no longer relevant. Moreover, BEL has only a minor effect on antigen- or thapsigargin-stimulated Ca2+ signalling, both the release from internal stores and sustained elevation due to Ca2+ influx. These results cast doubt on the proposed mechanism involving iPLA(2)beta required for Ca2+ entry. Although inhibition of exocytosis by BEL could imply a requirement for iPLA(2)beta activation for exocytosis, an alternative explanation is that BEL inactivates other target proteins required for exocytosis. (c) 2006 Elsevier Ltd. All rights reserved.

Type: Article
Title: Bromoenol lactone, an inhibitor of Group V1A calcium-independent phospholipase A(2) inhibits antigen-stimulated mast cell exocytosis without blocking Ca2+ influx
DOI: 10.1016/j.ceca.2006.06.002
Keywords: calcium entry, mast cells, IgE, thapsigargin, secretion, calcium ionophore, phospholipase A(2), MECHANISM-BASED DISCRIMINATION, ARACHIDONIC-ACID RELEASE, SMOOTH-MUSCLE-CELLS, P388D(1) MACROPHAGES, GUANINE-NUCLEOTIDES, INSULIN-SECRETION, LYSOPHOSPHATIDYLCHOLINE, GENERATION, RECEPTOR, IDENTIFICATION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > The Sainsbury Wellcome Centre
URI: http://discovery.ucl.ac.uk/id/eprint/182552
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