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Calcium ionophore A23187 induces release of chemokinetic and aggregating factors from polymorphonuclear leucocytes.

ABSTRACT: 1. Rat and human polymorphonuclear leucocytes (PMNs) when exposed to calcium ionophore A23187 10 microM release products which cause aggregation of rat PMNs and chemokinesis of human PMNs. 2. Aggregating and chemokinetic activities are rapidly generated; maximal release occurs after 4 min, and can be detected in dilutions of the supernatant of up to 1:1000. 3. Generation of aggregating and chemokinetic activities is inhibited by nordihydroguaiaretic acid 10(-4) to 10(0-7) M, 5,8,11,14-eicosatetraynoic acid 10(-4) and 10(-5) M, BW 755C 10(-4) M and benoxaprofen 10(-4) M, all compounds known to inhibit lipoxygenase pathways of arachidonic acid (AA) metabolism. 4. Conventional non-steroidal anti-inflammatory agents, such as aspirin and indomethacin, inhibited little or not at all the generation of these activities. 5. We conclude that the aggregating and chemokinetic activities induced by A23187 represent generation of biologically active products of lipoxygenase pathways of AA metabolism.

SUBMITTER: Bray MA

PROVIDER: S-EPMC2044478 | biostudies-other | 1980

REPOSITORIES: biostudies-other

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Calcium ionophore A23187 induces release of chemokinetic and aggregating factors from polymorphonuclear leucocytes.

Bray M A MA Ford-Hutchinson A W AW Shipley M E ME Smith M J MJ

British journal of pharmacology 19800101 2

1. Rat and human polymorphonuclear leucocytes (PMNs) when exposed to calcium ionophore A23187 10 microM release products which cause aggregation of rat PMNs and chemokinesis of human PMNs. 2. Aggregating and chemokinetic activities are rapidly generated; maximal release occurs after 4 min, and can be detected in dilutions of the supernatant of up to 1:1000. 3. Generation of aggregating and chemokinetic activities is inhibited by nordihydroguaiaretic acid 10(-4) to 10(0-7) M, 5,8,11,14-eicosatetr ...[more]

PMID: 6781577

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Project description:Stimulation of rabbit polymorphonuclear leucocytes with A23187 causes phospholipase C mediated breakdown of polyphosphoinositides, as evidenced by accumulation of [3H]inositol-labelled inositol bisphosphate and inositol trisphosphate. At the same time the polyphosphoinositides and the products of their breakdown, diacylglycerol and phosphatidic acid, label rapidly with radioactive arachidonic acid. Enhancement of polyphosphoinositide labelling is not as great as enhancement of diacylglycerol or phosphatidic acid labelling, suggesting additional early activation of a second independent synthetic pathway to the last named lipids. Experiments using double (3H/14C) labelling, to distinguish pools with different rates of turnover, suggest the major pool of arachidonic acid used for synthesis of lipoxygenase metabolites turns over more slowly than arachidonic acid in diacylglycerol, but at about the same rate as arachidonic acid esterified in phosphatidylcholine or phosphatidylinositol. Further, when cells are prelabelled with [14C]arachidonic acid, then stimulated for 5 min, it is only from phosphatidylcholine, and to a lesser extent phosphatidylinositol, that radiolabel is lost. Release of arachidonic acid is probably via phospholipase A2, since it is blocked by the phospholipase A2 inhibitor manoalide. The absence of accumulated lysophosphatides can be explained by reacylation and, in the case of lysophosphatidylinositol, deacylation. The importance of phospholipase A2 in phosphatidylinositol breakdown contrasts with the major role of phospholipase C in polyphosphoinositide hydrolysis. Measurements of absolute free fatty acid levels, as well as studies showing a correlation between production of radiolabelled hydroxyeicosatetraenoic acids and release of radiolabel from the phospholipid pool, both suggest that hydrolysis of arachidonic acid esterified into phospholipids is the limiting factor regulating formation of lipoxygenase metabolites. By contrast with A23187, fMet-Leu-Phe (a widely used polymorphonuclear leucocyte activator) is a poor stimulant for arachidonic acid release unless a 'second signal' (e.g. cytochalasin B, or a product of A23187-stimulated cells) is also present. In the presence of cytochalasin B, fMet-Leu-Phe, like A23187, stimulates release of radiolabelled arachidonic acid principally from phosphatidylcholine.

Dataset Information

Calcium ionophore A23187 induces release of chemokinetic and aggregating factors from polymorphonuclear leucocytes.

Publications

Calcium ionophore A23187 induces release of chemokinetic and aggregating factors from polymorphonuclear leucocytes.

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