Prostanoids

In asthmatic patients, it is likely that PGDinf2/inf and TinfX/infAinf2/inf are involved in causing acute bronchoconstriction after stimuli such as inhaled allergen in asthmatic patients. PGDinf2/inf 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 PGEinf2/inf release. PGDinf2/inf is released from stimulated dispersed human lung cells in vitro and from the airways of allergic human subjects, which have been stimulated by allergen. PGDinf2/inf synthase is present in mast cells, T helper 2 (TinfH/inf2) cells, and other leukocytes. PGDinf2/inf is rapidly metabolized (with a half-life of 1.5 min in blood), and the main byproducts that have been detected in vivo are PGJinf2/inf and 9 11 PGFinf2/inf. PGDinf2/inf is a bronchoconstrictor of human airways and is more potent when inhaled by human subjects than PGFinf2/inf. Finally, PGEinf2/inf can also attenuate allergen-induced airway responses and eosinophilic inflammation. These studies suggest that endogenous production of PGEinf2/inf does have an important influence on the magnitude of asthmatic responses to stimuli such as exercise or inhaled allergens.