Chemotactic for Human Granulocytes

A biologically active glutathione adduct of the eicosanoid 5-oxo-eicosatetraenoic acid has been observed as a product formed within the murine peritoneal macrophage. This five-oxo glutathione adduct (FOG 7 ) was structurally characterized using electrospray tandem mass spectrometry as a 1,4 Michael addition product 5-oxo-7-glutathionyl-8,11,14-eicosatrienoic acid. FOG 7 was found to be highly potent in stimulating eosinophil as well as neutrophil chemotaxis, also capable of initiating actin polymerization, without elevating intracellular free calcium ion concentration within either the eosinophil or polymorphonuclear leukocyte. These biological responses suggest that either FOG 7 activates a subset of receptors mediating the broader biological activity of the parent eicosanoid 5-oxo-ETE or that a receptor not activated by 5-oxo-ETE participates in the chemotactic activity of FOG 7 . The only other known biologically active glutathione adduct has been leukotriene C 4 , another eicosanoid which exerts potent effects through the cys-LT receptor. The biochemical parallel between the formation of LTC 4 and FOG 7 suggests an interesting mechanism by which biologically active eicosanoids derived from electrophilic intermediates may have unique distribution and prolonged efficacy in vivo. by gest on July 5, 2017 hp://w w w .jb.org/ D ow nladed from