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

J Clin Invest. 1999 Sep;104(6):721-32. doi: 10.1172/JCI6890.


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.

MeSH terms

  • Allergens / immunology
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Dinoprostone / biosynthesis
  • Female
  • Hypersensitivity / etiology*
  • Immunoglobulin E / analysis
  • Isoenzymes / deficiency
  • Isoenzymes / physiology*
  • Leukotriene B4 / biosynthesis
  • Lung / immunology*
  • Lung / pathology
  • Lung Compliance
  • Lysosomes / enzymology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Prostaglandin-Endoperoxide Synthases / deficiency
  • Prostaglandin-Endoperoxide Synthases / physiology*


  • Allergens
  • Isoenzymes
  • Leukotriene B4
  • Immunoglobulin E
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone