title: Chlorination of endogenous amines by isolated neutrophils. Ammonia-dependent bactericidal, cytotoxic, and cytolytic activities of the chloramines.
abstract: 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.
mesh_terms: D000588:Amines / Q000097:blood*; D000641:Ammonia / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D002700:Chloramines / Q000097:blood / Q000633:toxicity*; D002712:Chlorides / Q000097:blood*; D003594:Cytoplasmic Granules / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology*; D004926:Escherichia coli / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D007700:Kinetics; D007945:Leukemia, Lymphoid; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000588:Amines; D002700:Chloramines; D002712:Chlorides; D000641:Ammonia; D015054:Zymosan; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate