Mediator release from human lung under conditions of reduced oxygen tension

S. P. Peters, L. M. Lichtenstein, N. F. Adkinson

Research output: Contribution to journalArticlepeer-review

Abstract

Although the mechanism underlying hypoxic pulmonary vasoconstriction remains undefined, various reports have suggested that mast cells and mast cell-derived mediators may be important in the production of this phenomenon. We investigated the effect of reducing oxygen tension on the release from human lung fragments of the mast cell-derived mediators histamine, prostaglandin (PG) D2 and peptide leukotrienes, as well as the release of the largely non-mast cell-derived mediators PGE2, PGF(2α), prostacyclin metabolite (6-keto-PGF(1α)) and the thromboxane A2 metabolite (thromboxane B2). The effect of reducing oxygen tension on both basal mediator release and release triggered by goat antihuman immunoglobulin E was studied. Reducing pO2 of buffer in which lung fragments were placed from 161 to 54 mm Hg resulted in no spontaneous release of histamine, PGD2 or peptide leukotrienes. However, hypoxia had a marked effect on mediator release triggered by goat antihuman immunoglobulin E. Although net histamine release was relatively unaffected (control 13.9 ± 2.7%, hypoxic 12.7 ± 2.1%), hypoxic treatment resulted in an 89% inhibition of PGD2 release (control 47.7 ± 17.4 ng/g of lung, hypoxic 5.26 ± 1.91 ng/g of lung) and an 81% inhibition of peptide leukotriene release (control 22.5 ± 7.6 ng/g of lung, hypoxic 4.37 ± 2.4 ng/g of lung). Similar inhibition was seen for non-mast cell-derived mediators, including PGF(2α), prostacyclin metabolite and thromboxane B2, and probably for PGE2. We conclude that hypoxic treatment of human lung fragments in vitro results in no spontaneous release of preformed or newly formed mediators but that it markedly alters mediator release after goat antihuman immunoglobulin E triggering. Release of most oxygenated products of arachidonic acid was markedly inhibited, whereas the release of the preformed mediator histamine was largely unaffected.

Original languageEnglish (US)
Pages (from-to)8-13
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume238
Issue number1
StatePublished - 1986

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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