Effects of S-lactoylglutathione and inhibitors of glyoxalase I on histamine release from human leukocytes

THE enzyme responsible for the conversion of methylglyoxal to lactic acid by animal tissues was first named glyoxalase^1,2. It was later shown that there are two glyoxalase enzymes³. The first (glyoxalase I). converts methylglyoxal and reduced glutathione to S-lactoylglutathione and the second (glyoxalase II). converts this compound to uc(D)-lactic acid, regenerating glutathione in the process. These enzymes are very widely distributed⁴ and as yet have no clearly defined function(s). I describe here the enhancement of anti-IgE-induced histamine release by S-lactoylglutathione and its inhibition by an inhibitor of and an alternative substrate for glyoxalase I. These two compounds should, of course, decrease the production of endogenous S-lactoylglutathione. These experiments were undertaken for two reasons. First, a study from my laboratory has provided evidence that S-lactoylglutathione modulates microtubule assembly in vitro⁵ while the release of histamine from leukocytes is a secretory process thought to require an intact microtubule system^6,7. Second, concanavalin A has been shown to cause histamine release from human leukocytes^8,9 and has also been found to activate the two glyoxalase enzymes in lymphocytes and polymorphonuclear leukocytes¹⁰.