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 PGE2 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 PGE2 in wild-type mice. We conclude that (a) PGHS-1 is the predominant enzyme that biosynthesizes PGE2 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.
Stephen H. Gavett, Sharon L. Madison, Patricia C. Chulada, Paula E. Scarborough, Wei Qu, James E. Boyle, Howard F. Tiano, Christopher A. Lee, Robert Langenbach, Victor L. Roggli, Darryl C. Zeldin
Guidelines: The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. We reserve the right to edit any letter for length, content, and clarity. Authors will be notified by e-mail if their letters were accepted. No appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editors directly at firstname.lastname@example.org.