Meta-Biol

• Pathways

In human macrophages, a glutathione hydrolase (GGT) is proposed to cleave the γ-glutamyl moiety of MCTR1 to yield MCTR2, identified as 13(R)-cysteinylglycinyl, 14(S)-hydroxy-docosahexaenoic acid (Dalli et al. 2014, 2016a, 2016b). Incubation of human macrophages with MCTR1 and GGT enzyme inhibitors significantly reduces MCTR2 and MCTR3 production and significantly increases MCTR1 amounts, suggesting a GGT mediates MCTR2 production (Dalli et al. 2016a). In addition, Dalli et al. found the human recombinant GGT used in the experiment has a higher affinity for MCTR1 than leukotriene C4 (Dalli et al. 2016a). MCTR2, given to mice with E. coli peritonitis, showed potent proresolving action in inflammation and infections. With human macrophages, MCTR2 proved to be more potent that MCTR1 in stimulating efferocytosis of apoptotic cells (Dalli et al. 2014).