The chlorinating potential of the human monocyte

Abstract

Human monocytes incubated with phorbol myristate acetate (PMA) or opsonized zymosan particles can chlorinate the beta-amino acid taurine to its monochloramine derivative. Taurine monochloramine can then be quantitated by its ability to oxidize 5-thio-2-nitrobenzoic acid to its disulfide or by its characteristic absorption peak at 252 nm. Stimulated, but not resting, monocytes chlorinated taurine by a process dependent on time, cell concentration, and pH. The formation of taurine chloramine by stimulated monocytes could be inhibited by catalase, azide, or cyanide, was unaffected by superoxide dismutase, and was stimulated by exogenous myeloperoxidase. Thus, taurine chloramine generation by human monocytes appeared dependent on both H2O2 and myeloperoxidase. Compared to human neutrophils, the monocyte could generate similar amounts of chloramine when stimulated with phorbol myristate acetate, but far less if opsonized zymosan particles were used as the trigger. Based on the known ability of the H2O2- myeloperoxidase-Cl- system to generate free HOCl, it would seem that this oxidant is the most likely species responsible for the monocyte- mediated chlorination reactions. Thus, we have used a simple quantitative assay to demonstrate the ability of the human monocyte to generate large quantities of a highly reactive and toxic oxygen metabolite.

Antimicrobial Activity of Dexamethasone and Its Combination With N-Chlorotaurine

“…N-Chlorotaurine (ClHN-CH 2 -CH 2 -SO 3 H) is a weak oxidant, produced by human granulocytes and monocytes during inflammation. 1,2 It also can be synthesized chemically as a crystalline sodium salt and is highly soluble in aqueous solution, which enables its application as an antiseptic in human medicine. 3 It is microbicidal against a broad spectrum of all classes of pathogens, including bacteria and fungi.…”

Oxidation of low-density lipoprotein by hypochlorite causes aggregation that is mediated by modification of lysine residues rather than lipid oxidation

“…Upon appropriate stimulation, monocytes can release large amounts of myeloperoxidase (MPO, EC 1.11.1.7) into the extracellular space [10,11], although they lose this ability as they differentiate into macrophages [11]. MPO reacts with H202 to form, initially and transiently, compound I, which itself can react with Clions to form hypochlorite (-OC1) [12] or, depending on the availability of substrates, participate in one-electron reactions [13,14].…”

Human neutrophils employ the myeloperoxidase/hydrogen peroxide/chloride system to oxidatively damage apolipoprotein A‐I

“…The microbicidal activity of these cells, in particular neutrophils, depends on the interaction of a broad array of potent systems, including relatively stable degradative enzymes as well as labile reactive oxygen species. Activation of neutrophils and monocytes results in the formation of O 2 •– and H 2 O 2 and the release of the enzyme myeloperoxidase (MPO) [1], an enzyme that catalyzes the formation of hypochlorous acid/hypochlorite (HOCl/OCl − ) from H 2 O 2 and Cl − [2]. Neutrophil‐derived oxidants (in particular HOCl) react with a variety of different biological targets and can cause tissue damage.…”

“…Neutrophil‐derived oxidants (in particular HOCl) react with a variety of different biological targets and can cause tissue damage. The ability of HOCl to damage proteins [3], amino acids [4], lipids [5–7] and nucleic acids [8,9] is thought to contribute to bacterial killing [2] and the pathogenesis of disease [10–12].…”