PMID: 9422335Jan 9, 1998Paper

Regulation of leukotriene and platelet-activating factor synthesis in human alveolar macrophages

The Journal of Laboratory and Clinical Medicine
M ShamsuddinL J Smith

Abstract

It has been suggested that phospholipase A2 (PLA2) contributes to the regulation of leukotriene (LT) and platelet-activating factor (PAF) synthesis by controlling the release of their precursors, arachidonic acid (AA) and lysophosphatidylcholine (lysoPC), from membrane phospholipids. In rat alveolar macrophages (AMs), PLA2 appears to have a major role in LT synthesis but a more limited role in PAF synthesis. The present study was designed to define the role of PLA2 in LT and PAF synthesis in human AMs and determine whether differences exist between AMs obtained from normal subjects and those from patients with asthma. In the normal subjects, the calcium ionophore A23187 (Cal) increased AM PAF synthesis (percent incorporation of tritiated acetate) by 135% (p < 0.01) and LTB4 synthesis 88-fold (p < 0.001). Phorbol myristate acetate (PMA) had little effect alone, but it had a synergistic effect with Cal, increasing PAF synthesis by 466% and LTB4 synthesis to 229-fold above the control values (p < 0.001 for both). Ro 25-4331, a combined cytosolic (c) and secretory (s) PLA2 inhibitor, had little effect on the Cal-stimulated PAF synthesis, but it completely blocked the effect of PMA. It also blocked the Cal- and Cal+PMA-stimulated LT...Continue Reading

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Citations

Feb 15, 2000·American Journal of Respiratory and Critical Care Medicine·S T Holgate, A P Sampson
Sep 26, 2006·COPD·Peter J Barnes
Nov 24, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sarit OfferDavid Shoseyov
Dec 17, 2004·Pharmacological Reviews·Peter J Barnes
Dec 11, 1999·Proceedings of the Association of American Physicians·J M Drazen

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