Oxygen metabolites stimulate release of high-molecular-weight glycoconjugates by cell and organ cultures of rodent respiratory epithelium via an arachidonic acid-dependent mechanism.
Several common pulmonary disorders characterized by mucus hypersecretion and airway obstruction may relate to increased levels of inhaled or endogenously generated oxidants (O2 metabolites) in the respiratory tract. We found that O2 metabolites stimulated release of high-molecular-weight glycoconjugates (HMG) by respiratory epithelial cells in vitro through a mechanism involving cyclooxygenase metabolism of arachidonic acid. Noncytolytic concentrations of chemically generated O2 metabolites (purine + xanthine oxidase) stimulated HMG release by cell and explant cultures of rodent airway epithelium, an effect which is inhibitable by coaddition of specific O2 metabolite scavengers or inhibitors of arachidonic acid metabolism. Addition of O2 metabolites to epithelial cells provoked production of PGF2a, an effect also inhibitable by coaddition of O2 metabolite scavengers or inhibitors of arachidonic acid metabolism. Finally, addition of exogenous PGF2a to cell cultures stimulated HMG release. We conclude that O2 metabolites increase release of respiratory HMG through a mechanism involving cyclooxygenase metabolism of arachidonic acid with production mainly of PGF2a. This mechanism may be fundamental to the pathogenesis of a variety of lung diseases associated with hypersecretion of mucus and/or other epithelial fluids, as well as a basic cellular response to increased oxidants.
Adler
K B
KB
Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Holden-Stauffer
W J
WJ
Repine
J E
JE
D000818:Animals; D001095:Arachidonic Acids / Q000302:isolation & purification / Q000378:metabolism*; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006001:Glycoconjugates / Q000378:metabolism*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009924:Organ Culture Techniques; D011092:Polyethylene Glycols / Q000494:pharmacology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism
D001095:Arachidonic Acids; D006001:Glycoconjugates; D013481:Superoxides; D008353:Mannitol; D011092:Polyethylene Glycols; C038983:1,3-dimethylthiourea; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D013890:Thiourea