Biosynthesis of Prostaglandins by Isolated and Cultured Airway Epithelial Cells

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Abstract
The metabolism of arachidonic acid to prostaglandins and thromboxane by freshly isolated and cultured respiratory tract epithelial cells was examined by HPLC methods. Homogenates prepared from freshly isolated rat and rabbit tracheal epithelial cells did not convert arachidonic acid to prostaglandins. Rat tracheal epithelial cells however, did convert arachidonic acid to uncharacterized metabolites possibly hydroxyfatty acids. In contrast, rat tracheal epithelial cells grown in culture for 9 days acquired the capacity to convert arachidonic acid to PGE2 and related products while cultured rabbit tracheal epithelial cells converted arachidonic acid to TXB2. The conversion of arachidonic acid to PGE2 by rat tracheal cells was studied at various times in culture. The formation of PGE2 appeared to parallel the growth of the cultures. In contrast to freshly isolated rat tracheal cells, enriched rat Clara cell fractions were able to convert 14C-arachidonic acid to prostacyclin (PGI2) ans measured by HPLC analysis of its stable end product 6-keto PGF1 alpha. PGI2 was also the major metabolite of arachidonic acid produced by enriched rat alveolar type II cell fractions. PGF2 alpha, and hydroxyfatty acids were also formed. These results suggest that arachidonic acid metabolism differs in various types of respiratory tract cells and that maintenance of such cells in culture alters the pattern of arachidonic acid metabolism.