Thiocyanate Is an Efficient Endogenous Scavenger of the Phagocytic Killing Agent Hypobromous Acid

Abstract

Second-order rate constants for the reaction of HOBr/OBr- (a putative killing agent of eosinophils and a reactive oxygen species that is implicated in mutagenesis and in human inflammatory diseases) with SCN- (an endogenous species in human physiologic fluids) are determined by stopped-flow spectroscopy. The proposed mechanism includes parallel pathways with Br+ transfer to SCN- by general acid catalysis and by direct reaction with HOBr. HOBr reacts with SCN- with a second-order rate constant (2.3 x 10(9) M(-1) s(-1)) that is 2 orders of magnitude larger than that previously measured for the reaction of HOCl with SCN- (2.3 x 10(7) M(-1) s(-1)), and very close to the diffusion limit. In contrast to OCl-, OBr- exhibits a measurable rate of reaction with SCN- (3.8 x 10(4) M(-1) s(-1)). On a molar basis, SCN- is the most effective scavenger of HOBr to be reported to date (200 times more effective than cysteine and 650 times more effective than methionine). Computational models suggest that SCN- is competitive with respect to other scavengers at physiologically relevant concentrations, which leads us to propose it may limit the lifetime of HOBr and its propensity to inflict host tissue damage during inflammatory response, especially during eosinophilia. Furthermore, the product of the nonenzymatic reaction of HOBr and SCN-, hypothiocyanite (OSCN-), is an effective antimicrobial that is relatively innocuous toward mammalian cell lines. Since one of the principal charges of eosinophil cells is to clear extracellular parasites via nonphagocytic mechanisms that involve degranulation of eosinophil peroxidase (EPO, the principal mammalian enzyme that produces HOBr), a larger role for OSCN- is suggested for parasitic infection.