Chlorination of endogenous amines by isolated neutrophils. Ammonia-dependent bactericidal, cytotoxic, and cytolytic activities of the chloramines.

Isolated human neutrophilic leukocytes were stimulated to produce hydrogen peroxide (H2O2) and to secrete cytoplasmic granule components including myeloperoxidase into the medium. Myeloperoxidase catalyzed the oxidation of chloride (Cl-) by H2O2 to yield hypochlorous acid (HOCl), which reacted with endogenous nitrogen compounds to yield derivatives containing nitrogen-chlorine (N-Cl) bonds. Compounds available for reaction with HOCl were ammonia (NH+4), taurine, alpha-amino acids, and granule proteins and peptides that were released into the medium. A portion of the N-Cl derivatives formed under these conditions accumulated in the extracellular medium. These long lived oxidizing agents were characterized as hydrophilic, low molecular weight, mono-N-chloramine (RNHCl) derivatives based on their absorption spectrum, ability to oxidize 5-thio-2-nitrobenzoic acid and to chlorinate ammonia (NH+4), and behavior upon ultrafiltration, gel chromatography, and extraction with organic solvents. The RNHCl derivatives were of low toxicity, but reacted with NH+4 to yield the lipophilic oxidizing agent monochloramine (NH2Cl). Therefore, the addition of NH+4 conferred bactericidal, cytotoxic, and cytolytic activities on the RNHCl derivatives. The results indicate that taurine and other neutrophil amines protect neutrophils and other cells against oxidative attack by acting as a trap for HOCl and by competing with endogenous NH+4 for reaction with HOCl. However, the RNHCl derivatives act as a reserve of oxidizing equivalents that is converted to a toxic form when an increase in NH+4 concentration favors formation of NH2Cl.