Allergic lung responses are increased in prostaglandin H synthase-deficient mice.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gavett, SH; Madison, SL; Chulada, PC; Scarborough, PE; Qu, W; Boyle, JE; Tiano, HF; Lee, CA; Langenbach, R; Roggli, VL; Zeldin, DC

Published Date

  • September 1999

Published In

Volume / Issue

  • 104 / 6

Start / End Page

  • 721 - 732

PubMed ID

  • 10491407

Pubmed Central ID

  • 10491407

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI6890

Language

  • eng

Conference Location

  • United States