EFFECT OF PROSTAGLANDIN E(2) ON EICOSANOID RELEASE BY HUMAN BRONCHIALBIOPSY SPECIMENS FROM NORMAL AND INFLAMED MUCOSA

Background - Eicosanoids such as prostaglandin E(2) (PGE(2)) thromboxa ne A(2) (TXA(2)), and peptidoleukotrienes (pLT) are known to be biolog ically highly active lipid mediators, especially in human lung epithel ium. PGE(2) is thought to have mostly bronchoprotective effects, where as pLT and TXA(2) are bronchoconstrictive. This study was undertaken t o assess the release and interaction of eicosanoids in human bronchial biopsy specimens of normal and inflamed mucosa.Methods - Bronchial bi opsy specimens were obtained from 16 patients, seven controls without signs of inflammation and nine patients with severe inflammatory proce sses in the epithelium. The release of pLT, TXA(2) (measured as TXB(2) ), and PGE(2) was investigated using a ''functional in vitro test'' an d the addition of several stimuli. Results - Specimens incubated with arachidonic acid released higher amounts of pLT, TXB(2), and PGE(2) th an unstimulated specimens. Preincubation with PGE(2) revealed signific ant inhibition of arachidonic acid-induced release of pLT and TXB(2) ( > 50%). The inhibitory effect was higher in normal than in inflamed ep ithelium. Conclusions - Exogenous PGE(2) has inhibitory effects on the release of pLT and TXB(2) in human bronchial biopsy specimens. This f inding could explain the bronchoprotective effect of inhaled PGE, in n ormal subjects and asthmatic subjects as direct eicosanoid interaction s. It also supports the concept of PGE(2) as a bronchoprotective endog enous substance. The complex effects of PGE(2) as a modulating mediato r in inflammation may be worth investigating.