The pharmacologic modulation of the release of arachidonic acid metabolites from purified human lung mast cells

S. P. Peters, D. W. MacGlashan, R. P. Schleimer, E. C. Hayes, N. F. Adkinson, L. M. Lichtenstein

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35 Scopus citations

Abstract

Although cyclooxygenase and lipoxygenase inhibitors have been widely used in studies of allergic and inflammatory disorders, the effect of these agents has not been determined on mediators released from purified human lung mast cells. The release of histamine, prostaglandin D2, leukotriene C4, leukotriene B isomers, 5-hydroxyeicosatetraenoic acid (5-HETE), and free arachidonic acid (AA) from preparations of purified human lung mast cells (90 ± 2% pure) prelabeled with 3H-AA as modified by indomethacin, eicosatriynoic acid (ETI), and diethylcarbamazine (DEC) was determined. Indomethacin (3 μM) markedly (>90%) inhibited the anti-IgE- and ionophore A23187-induced release of PGD2 from these cells but had no effect on the release of histamine or other AA metabolites. Specifically, no increase in LTC production was noted, and no large amounts of shunting or products into those produced by lipoxygenase was noted. The ETI, a lipoxygenase inhibitor in many systems, inhibited the release of histamine, PGD2, LTC, LTB isomers, 5-HETE, and free AA, all with an IC50 between 3 and 10 μM. The lack of specificity for lipoxygenase products together with a similar potency for inhibition of histamine release suggests that ETI may act at an early event in the activation process of these cells, apparently prior to the action of phospholipase(s), which releases AA from cellular stores. The DEC inhibited PGD2 release in purified mast cells and histamine release in pure and crude preparations of mast cells, both with IC50 values ranging from 1 to 3 mM. No specificity for enzymes responsible for the production of LTA4 was observed in these cells, unlike the results reported in other systems. In the case of all 3 agents studied, differences from those that might have been predicted on the basis of previous information were observed.

Original languageEnglish (US)
Pages (from-to)367-373
Number of pages7
JournalAmerican Review of Respiratory Disease
Volume132
Issue number2
StatePublished - 1985

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Peters, S. P., MacGlashan, D. W., Schleimer, R. P., Hayes, E. C., Adkinson, N. F., & Lichtenstein, L. M. (1985). The pharmacologic modulation of the release of arachidonic acid metabolites from purified human lung mast cells. American Review of Respiratory Disease, 132(2), 367-373.