Prostanoids

In asthmatic patients, it is likely that PGD2 and TXA2 are involved in causing acute bronchoconstriction after stimuli such as inhaled allergen in asthmatic patients. PGD2 also promotes the chemotaxis of eosinophils and Th2 cells, as well as the release of Th2 cytokines through stimulation of CRTH2. Also, there is evidence that inhibitory prostaglandins are released by asthmatic airways, which reduces bronchoconstrictor responses to stimuli such as exercise, and that this effect is mediated by leukotriene-induced PGE2 release. PGD2 is released from stimulated dispersed human lung cells in vitro and from the airways of allergic human subjects, which have been stimulated by allergen. PGD2 synthase is present in mast cells, T helper 2 (TH2) cells, and other leukocytes. PGD2 is rapidly metabolized (with a half-life of 1.5 min in blood), and the main byproducts that have been detected in vivo are PGJ2 and 9 α 11 β PGF2. PGD2 is a bronchoconstrictor of human airways and is more potent when inhaled by human subjects than PGF2. Finally, PGE2 can also attenuate allergen-induced airway responses and eosinophilic inflammation. These studies suggest that endogenous production of PGE2 does have an important influence on the magnitude of asthmatic responses to stimuli such as exercise or inhaled allergens. © 2009 Elsevier Ltd All rights reserved.