Protective Effects of Prostaglandin E2 on Pulmonary Vascular Remodeling in Allergic Airway Inflammation
Wei Xing, Anders Lundequist, Chunli Feng, Tao Liu, Joshua A Boyce. University of Massachusetts Medical School, Worcester, MA; Brigham and Women's Hospital, Boston, MA
Background: Nonselective inhibition of prostaglandin synthesis augments inflammation in mouse models of airway disease, but the roles of individual prostaglandin are not completely clarified. To investigate the role of PGE2 in a mouse model of airway inflammation induced by a natural allergen, we used mice lacking the critical terminal synthetic enzyme, microsomal PGE2 synthase (mPGES)-1.
Design: Mice lacking mPGES-1 (ptges-/- mice) and wild-type C57BL/6 controls were challenged intranasally with low doses of an extract derived from the house dust mite Dermatophagoides farinae (Der f). Pulmonary inflammation was evaluated by analysis of bronchoalveolar lavage fluid and histology.
Results: The levels of PGE2 in the bronchoalveolar lavage fluids of Der f-treated ptges-/- mice were ∼ 80% lower than the levels in wild-type controls. Both the extent of inflammation and goblet cell metaplasia were modestly increased in the Der f-treated ptges-/- mice compared with the WT controls. Unexpectedly, the numbers of vascular smooth muscle cells and the thickness of intrapulmonary vessels were both markedly increased in the Der f-treated ptges-/- mice. Immunofluorescent staining revealed ICAM-1 expression in the alveolar capillary endothelium was upregulated in the ptges-/- mice. Additionally, these vascular changes were suppressed by the administration of the stable PGE2 analog 16, 16-dimethyl PGE2.
Conclusions: PGE2 is known to be a direct vasodilator by relaxing smooth muscles. Our findings revealed that mPGES-1-derived PGE2 is essential to protect the lung vasculature from remodeling with inflammation. Upregulation of ICAM-1 expression in endothelium plays an important role in vascular remodeling by potentiating pulmonary inflammation in ptges-/- mice.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 307, Wednesday Morning