BACKGROUND: Eicosanoids such as prostaglandin E2 (PGE2), thromboxane A2 (TXA2), and peptidoleukotrienes (pLT) are known to be biologically highly active lipid mediators, especially in human lung epithelium. PGE2 is thought to have mostly bronchoprotective effects, whereas pLT and TXA2 are bronchoconstrictive. This study was undertaken to assess the release and interaction of eicosanoids in human bronchial biopsy specimens of normal and inflamed mucosa. METHODS: Bronchial biopsy specimens were obtained from 16 patients, seven controls without signs of inflammation and nine patients with severe inflammatory processes in the epithelium. The release of pLT, TXA2 (measured as TXB2), and PGE2 was investigated using a "functional in vitro test" and the addition of several stimuli. RESULTS: Specimens incubated with arachidonic acid released higher amounts of pLT, TXB2, and PGE2 than unstimulated specimens. Preincubation with PGE2 revealed significant inhibition of arachidonic acid-induced release of pLT and TXB2 (> 50%). The inhibitory effect was higher in normal than in inflamed epithelium. CONCLUSIONS: Exogenous PGE2 has inhibitory effects on the release of pLT and TXB2 in human bronchial biopsy specimens. This finding could explain the bronchoprotective effect of inhaled PGE2 in normal subjects and asthmatic subjects as direct eicosanoid interactions. It also supports the concept of PGE2 as a bronchoprotective endogenous substance. The complex effects of PGE2 as a modulating mediator in inflammation may be worth investigating.
BACKGROUND:Eicosanoids such as prostaglandin E2 (PGE2), thromboxane A2 (TXA2), and peptidoleukotrienes (pLT) are known to be biologically highly active lipid mediators, especially in human lung epithelium. PGE2 is thought to have mostly bronchoprotective effects, whereas pLT and TXA2 are bronchoconstrictive. This study was undertaken to assess the release and interaction of eicosanoids in human bronchial biopsy specimens of normal and inflamed mucosa. METHODS: Bronchial biopsy specimens were obtained from 16 patients, seven controls without signs of inflammation and nine patients with severe inflammatory processes in the epithelium. The release of pLT, TXA2 (measured as TXB2), and PGE2 was investigated using a "functional in vitro test" and the addition of several stimuli. RESULTS: Specimens incubated with arachidonic acid released higher amounts of pLT, TXB2, and PGE2 than unstimulated specimens. Preincubation with PGE2 revealed significant inhibition of arachidonic acid-induced release of pLT and TXB2 (> 50%). The inhibitory effect was higher in normal than in inflamed epithelium. CONCLUSIONS: Exogenous PGE2 has inhibitory effects on the release of pLT and TXB2 in human bronchial biopsy specimens. This finding could explain the bronchoprotective effect of inhaled PGE2 in normal subjects and asthmatic subjects as direct eicosanoid interactions. It also supports the concept of PGE2 as a bronchoprotective endogenous substance. The complex effects of PGE2 as a modulating mediator in inflammation may be worth investigating.
Authors: J W Weiss; J M Drazen; N Coles; E R McFadden; P F Weller; E J Corey; R A Lewis; K F Austen Journal: Science Date: 1982-04-09 Impact factor: 47.728
Authors: E A Ham; D D Soderman; M E Zanetti; H W Dougherty; E McCauley; F A Kuehl Journal: Proc Natl Acad Sci U S A Date: 1983-07 Impact factor: 11.205
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