Transcellular synthesis of cysteinyl-leukotrienes: From isolated cells to complex organ system (part 1)

complex organ system (part 1) Cysteinyl-leukotriene (Cys-LT) formation either may proceed through activation of a single cell type, possessing both 5-lipoxygenase and leukotriene (LT) C4 synthase enzymatic activities (direct synthesis), or it may involve the participation of different cell types whereby donor cells (ie, polymorphonuclear leukocytes [PMNLs]) possessing 5-lipoxygenase activity synthesize and transfer the unstable intermediate LTA4 to acceptor cells (ie, endothelial cells) possessing LTC4 synthase activity only (transcellular synthesis) . This process suggests that the cellular environment (ie, cell to cell interactions) is an important control in the production of eicosanoids.Quantitative analysis of 5-lipoxygenase metabolites showed that intact LTA4 is the main product released by PMNL on challenge with A23187 . It is, therefore, clear that the transcellular synthesis of cys-LT may be a quantitatively relevant phenomenon, resulting in substantial changes of the profile of 5-lipoxygenase metabolites produced on activation of a specific cellular species.

A number of studies have addressed the issue of trans-cellular synthesis of cys-LT by using different combinations of isolated cells . Fewer studies have addressed this topic by using isolated organ systems perfused with PMN. The latter approach, though more complex, provides the best conditions for PMNL-endothelial cell cooperation. Adhesion of activated PMNL to endothelial cells may indeed result in optimal transfer of PMNL-derived LTA4 to endothelial cells.

This entry was posted in Cardiology and tagged 5-Lipoxygenase inhibition, BAYX1005, Cysteinyl-leukotrienes.