Generation of nitrogen-chlorine oxidants by human phagocytes.

Test, Samuel T.; Lampert, Mark B.; Ossanna, P J; Thoene, Jess G.; Weiss, Stephen J.

doi:10.1172/jci111544

Cited by 150 publications

(69 citation statements)

References 26 publications

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“…It is thought that a significant fraction of the HOCl produced by the MPO system of activated neutrophils may react with endogenous amines (e.g., ammonia, taurine, and other amino acids) to yield derivatives containing nitrogen-chlorine bonds (12,19). In contrast to an earlier study (21), we find that the bactericidal potency of NH 2 Cl is slightly less, rather than more, when compared with that of HOCl.…”

Section: Vol 178 1996contrasting

confidence: 97%

Bacterial glutathione: a sacrificial defense against chlorine compounds

Chesney¹,

Eaton²,

Mahoney³

1996

J Bacteriol

140

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Aerobic organisms possess a number of often overlapping and well-characterized defenses against common oxidants such as superoxide and hydrogen peroxide. However, much less is known of mechanisms of defense against halogens such as chlorine compounds. Although chlorine-based oxidants may oxidize a number of cellular components, sulfhydryl groups are particularly reactive. We have, therefore, assessed the importance of intracellular glutathione in protection of Escherichia coli cells against hydrogen peroxide, hypochlorous acid, and chloramines. Employing a glutathione-deficient E. coli strain (JTG10) and an otherwise isogenic glutathione-sufficient E. coli strain (AB1157), we find that glutathione-deficient organisms are approximately twice as sensitive to killing by both hydrogen peroxide and chlorine compounds. However, the mode of protection by glutathione in these two cases appears to differ: exogenous glutathione added to glutathione-deficient E. coli in amounts equal to those which would be present in a similar suspension of the wild-type bacteria fully restored resistance of glutathione-deficient bacteria to chlorine-based oxidants but did not change resistance to hydrogen peroxide. Furthermore, in protection against chlorine compounds, oxidized glutathione is almost as effective as reduced glutathione, implying that the tripeptide and/or oxidized thiol undergo further reactions with chlorine compounds. Indeed, in vitro, 1 mol of reduced glutathione will react with ϳ3.5 to 4.0 mol of hypochlorous acid. We conclude that glutathione defends E. coli cells against attack by chlorine compounds and hydrogen peroxide but, in the case of the halogen compounds, does so nonenzymatically and sacrificially.Aerobic organisms have numerous and often redundant defenses against oxidants. The natural abundance of superoxide (O 2 Ϫ ) and hydrogen peroxide (H 2 O 2 ) makes superoxide dismutase, catalase, and peroxidases preeminently important oxidant defenses. These enzymatic systems, along with antioxidants such as tocopherols, retinoids, and ascorbate, provide effective protection against reasonable challenges with activated oxygen species. There are, however, other oxidants against which no obvious defenses are known. Important among these are the chlorine compounds hypochlorous acid (HOCl), monochloramine (NH 2 Cl), and taurine monochloramine, which are generated by mammalian neutrophils (10,20,27). Hypochlorous acid, in particular, is a strong electrophile and will oxidize a large number of biological molecules, especially those containing thiols, thioethers, and conjugated double bonds (5,25).Therefore, it is no surprise that both mammalian neutrophils and water treatment facilities use chlorine and its reactive derivatives as effective bactericides (22). In tests on dilute bacterial suspensions (free of other organics), HOCl has a 50% lethal dose (LD 50 ) of 0.2 to 3.0 M against most bacteria tested, and there is evidence that chlorine generated by the mammalian neutrophil myeloperoxidase (MPO)-H 2 O 2 -chloride syst...

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Section: Vol 178 1996contrasting

confidence: 97%

Bacterial glutathione: a sacrificial defense against chlorine compounds

Chesney¹,

Eaton²,

Mahoney³

1996

J Bacteriol

140

View full text Add to dashboard Cite

show abstract

“…Preincubating L-serine with HOCl avoided competing reactions (e.g., with amino residues on the RNase A that also might consume HOCl; refs. 22,23). For modification with the myeloperoxidase system, 60 nM myeloperoxidase, 1 mM L-serine, 1 mM H 2 O 2 , and 150 mM NaCl were incubated in buffer A at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…It involves myeloperoxidase, a heme protein secreted by activated phagocytes (19). This enzyme uses H2O2, which phagocytes also secrete, to convert chloride ion to hypochlorous acid (HOCl) (19)(20)(21) The initial product of the myeloperoxidase-H 2 O 2 -chloride system, HOCl, reacts with the amino group (RNH 2 ) of free amino acids to form a chloramine (RNHCl) (19,(22)(23)(24)(25):…”

mentioning

confidence: 99%

The myeloperoxidase system of human phagocytes generates Nε-(carboxymethyl)lysine on proteins: a mechanism for producing advanced glycation end products at sites of inflammation

Anderson¹,

Requena²,

Crowley³

et al. 1999

J. Clin. Invest.

328

219

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“…Hypochlorous acid/ hypochlorite can react with other molecules to form a variety of chlorinated oxidants (8). At least half of the neutrophil-derived chloramines result from the reaction ofHOCI/OCI-with endogenous taurine (9). Although taurine is generally thought of as an antioxidant, previous studies have demonstrated that even in the presence of high concentrations of taurine, the transformation of HOCI/OCI-to taurine chloramines does not reduce the oxidative potential of HOCI/OCl-against various chemical groups such as thiols and thioethers (10).…”

Section: Introductionmentioning

confidence: 99%

Taurine modulation of hypochlorous acid-induced lung epithelial cell injury in vitro. Role of anion transport.

Cantin¹

1994

J. Clin. Invest.

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Airway secretions of cystic fibrosis patients were found to contain high concentrations oftaurine, which decreased with antibiotic therapy during acute respiratory exacerbations. Taurine, in a 1:1 molar ratio with HOCl/OCl-, caused a 10-fold increase in the amount of HOCI/OCI needed to induce cytotoxicity to the cat lung epithelial cell line, AKD. Although DMSO protected cells against HOCl/OC--mediated injury, the presence of an equimolar concentration of taurine with HOCI/ OC-prevented DMSO from protecting cells and sulfhydryl groups against oxidation, suggesting the formation of taurine chloramines. Spectral properties confirmed the formation of monochloramines and dichloramines. Chloride-free buffer, DIDS, and low temperature (4°C) each protected the cells against taurine/HOCI/OClP, indicating that taurine chloramine uptake through anion transport pathways was required to induce cytotoxicity. A molar excess of taurine inhibited cytotoxicity, by decreasing taurine dichloramines and increasing the formation of less toxic taurine monochloramines. We conclude that taurine can protect lung epithelial cells by converting HOCl/OCI-to anionic monochloramines, but that taurine dichloramines can be toxic to respiratory epithelial cells through mechanisms that depend upon epithelial cell anion transport. (J. Clin. Invest. 1994. 93:606-614.)

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Generation of nitrogen-chlorine oxidants by human phagocytes.

Cited by 150 publications

References 26 publications

Bacterial glutathione: a sacrificial defense against chlorine compounds

Bacterial glutathione: a sacrificial defense against chlorine compounds

The myeloperoxidase system of human phagocytes generates Nε-(carboxymethyl)lysine on proteins: a mechanism for producing advanced glycation end products at sites of inflammation

Taurine modulation of hypochlorous acid-induced lung epithelial cell injury in vitro. Role of anion transport.

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