Cyclooxygenase metabolism of endogenous arachidonic acid by cultured human tracheal epithelial cells

L. Churchill, F. H. Chilton, J. H. Resau, R. Bascom, W. C. Hubbard, D. Proud

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

The epithelial cell may contribute to the regulation of pulmonary function during inflammatory diseases of the airways by producing metabolites of arachidonic acid (AA). We have used human tracheal epithelial cells (HTE), grown in serum-free medium, to examine cyclooxygenase metabolism of endogenous AA by these cells. Gas chromatography-negative ion mass spectrometry demonstrated that, regardless of stimulus (buffer, bradykinin, or the calcium ionophore A23187), epithelial cells produce PGE2 and PGF(2α) but no detectable levels of PGD2, thromboxane B2, 6-keto-PGF(1α), or 9α,11β-PGF2. Preincubation of cultures with medium containing 5% human serum led to striking increases in the production of PGE2 and PGF(2α), regardless of stimulus. Concomitant with these increases in prostanoids, serum exposure caused a 3.6-fold increase in total cellular arachidonate. Arachidonate levels increased in all phosphoglyceride classes, with the greatest increases in phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol. In serum-pretreated cells, PGE2 production was 1.46 ± 0.12, 4.74 ± 0.6, and 6.35 ± 0.93 ng/106 cells (mean ± SEM; n = 7) upon exposure to buffer, 10-6 M bradykinin, and 1 μg/ml A23187, respectively, whereas PGF(2α) levels were 1.53 ± 0.22, 4.44 ± 0.36, and 5.77 ± 0.78 ng/106 cells, respectively. The response to HTE to bradykinin was dose-dependent (10-8 to 10-6 M) and was maximal within 5 min. We conclude that cyclooxygenase metabolism of endogenous arachidonate in HTE results in the specific production of PGE2 and PGF(2α). HTE in culture retain receptors for bradykinin and can be used to study lipid metabolism independent of other cell types.

Original languageEnglish (US)
Pages (from-to)449-459
Number of pages11
JournalAmerican Review of Respiratory Disease
Volume140
Issue number2 I
DOIs
StatePublished - 1989

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

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