'Lox on neovascularization': leukotrienes as mediators in endothelial biology.

摘要

Leukotrienes comprise the 5-lipoxygenase (5-LOX)-derived family of short-lived lipid mediators that modulate inflammatory cell reactivity and vascular function under both physiological and pathophysiological conditions (for overview, see Poeckel and Funk ). The leukotriene LTA4 is synthesized from arachidonic acid by 5-LOX in conjunction with 5-LOX-activation protein (FLAP; Figure 1A). Next, LTA4 is converted by LTA4 hydrolase to LTB_4, or by LTC_4 synthase to LTC_4, which through hydrolysis can give rise to LTD4 and LTE_4, respectively. BLT_(1/2) and CysLT_(1/2) are the main leukotriene receptors that specifically bind the respective leukotriene LTB_4 and the cysteinyl leukotrienes LTC_4, LTD_4, and LTE_4. Upon activation, both BLT and CysLT activate a G-protein response (via G_q and G_1), eliciting a potent increase in intracellular calcium levels and a decrease in cyclic AMP levels, and initiating kinase activation (i.e. ERK.1/2) and cellular responses such as differentiation, migration, and chemotaxis (Figure 78).