title: Allergic lung responses are increased in prostaglandin H synthase-deficient mice.
abstract: To investigate the function of prostaglandin H synthase-1 and synthase-2 (PGHS-1 and PGHS-2) in the normal lung and in allergic lung responses, we examined allergen-induced pulmonary inflammation and airway hyperresponsiveness in wild-type mice and in PGHS-1(-/-) and PGHS-2(-/-) mice. Among nonimmunized saline-exposed groups, we found no significant differences in lung function or histopathology, although PGE(2) was dramatically reduced in bronchoalveolar lavage (BAL) fluid from PGHS-1(-/-) mice, relative to wild-type or PGHS-2(-/-) mice. After ovalbumin sensitization and challenge, lung inflammatory indices (BAL cells, proteins, IgE, lung histopathology) were significantly greater in PGHS-1(-/-) mice compared with PGHS-2(-/-) mice, and both were far greater than in wild-type mice, as illustrated by the ratio of eosinophils in BAL fluid (8:5:1, respectively). Both allergic PGHS-1(-/-) and PGHS-2(-/-) mice exhibited decreased baseline respiratory system compliance, whereas only allergic PGHS-1(-/-) mice showed increased baseline resistance and responsiveness to methacholine. Ovalbumin exposure caused a modest increase in lung PGHS-2 protein and a corresponding increase in BAL fluid PGE(2) in wild-type mice. We conclude that (a) PGHS-1 is the predominant enzyme that biosynthesizes PGE(2) in the normal mouse lung; (b) PGHS-1 and PGHS-2 products limit allergic lung inflammation and IgE secretion and promote normal lung function; and (c) airway inflammation can be dissociated from the development of airway hyperresponsiveness in PGHS-2(-/-) mice.
authors.affiliation: Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Gavett
authors.forename: S L
authors.initials: SL
authors.lastname: Madison
authors.forename: P C
authors.initials: PC
authors.lastname: Chulada
authors.forename: P E
authors.initials: PE
authors.lastname: Scarborough
authors.forename: W
authors.initials: W
authors.lastname: Qu
authors.forename: J E
authors.initials: JE
authors.lastname: Boyle
authors.forename: H F
authors.initials: HF
authors.lastname: Tiano
authors.forename: C A
authors.initials: CA
authors.lastname: Lee
authors.forename: R
authors.initials: R
authors.lastname: Langenbach
authors.forename: V L
authors.initials: VL
authors.lastname: Roggli
authors.forename: D C
authors.initials: DC
authors.lastname: Zeldin
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D006967:Hypersensitivity / Q000209:etiology*; D007073:Immunoglobulin E / Q000032:analysis; D007527:Isoenzymes / Q000172:deficiency / Q000502:physiology*; D007975:Leukotriene B4 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008170:Lung Compliance; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000502:physiology*
chemical_list: D000485:Allergens; D007527:Isoenzymes; D007975:Leukotriene B4; D007073:Immunoglobulin E; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone