Myeloperoxidase-dependent effect of amines on functions of isolated neutrophils

Edwin Thomas, M. B. Grisham, M. M. Jefferson

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

Isolated neutrophilic leukocytes were incubated with primary amines and related nitrogenous compounds. Stimulation of neutrophil oxygen (O2) metabolism with phorbol myristate acetate or opsonized zymosan resulted in production of hydrogen peroxide (H2O2), myeloperoxidase-catalyzed oxidation of chloride (Cl-) to hypochlorous acid (HOCl), and the reaction of HOCl with the added compounds to yield nitrogen-chlorine (N-Cl) derivatives. Formation of N-Cl derivatives of low lipid solubility resulted in accumulation of the derivatives in the extracellular medium. These oxidizing agents were identified and measured on the basis of their absorption spectra and their ability to oxidize 5-thio-2-nitrobenzoic acid to the disulfide form. The yield of N-Cl derivatives was in the order: taurine > Tris > spermidine > spermine > glucosamine > putrescine > guanidinoacetate. Accumulation of N-Cl derivatives was also observed in the absence of added amines, owing to the reaction of HOCl with endogenous taurine and other amines that were released from the cells into the medium. In the presence of compounds that yield lipophilic N-Cl derivatives, little or no accumulation of oxidizing agents was observed. Instead, these compounds inhibited the accumulation of N-Cl derivatives that was obtained with taurine, and their effect was competitive with taurine. Inhibition was in the order: methylamine > ethanolamine > phenylethylamine > p-toluenesulfonamide > ammonia > guanidine. Formation of lipophilic N-Cl derivatives also resulted in inhibition of O2 uptake and glucose metabolism. Inhibition was prevented by adding catalase to eliminate H2O2, dapsone to inhibit myeloperoxidase, taurine to compete for reaction with HOCl, or compounds that are rapidly oxidized by HOCl or N-Cl derivatives, to reduce these oxidizing agents. The results indicate that: (a) formation of N-Cl derivatives that do not penetrate biological membranes can protect leukocytes against the cytotoxicity of HOCl and lipophilic N-Cl derivatives, and (b) formation of membrane-permeable N-Cl derivatives in the absence of target cells or readily oxidized substances results in oxidative attack by the N-Cl derivatives on leukocyte components and inhibition of leukocyte functions.

Original languageEnglish (US)
Pages (from-to)441-454
Number of pages14
JournalJournal of Clinical Investigation
Volume72
Issue number2
DOIs
StatePublished - Jan 1 1983

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Chlorine
Peroxidase
Amines
Neutrophils
Nitrogen
Hypochlorous Acid
Taurine
Leukocytes
Oxidants
Phenethylamines
Dapsone
Ethanolamine
Zymosan
Putrescine
Spermidine
Membranes
Spermine
Glucosamine
Guanidine
Tetradecanoylphorbol Acetate

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Myeloperoxidase-dependent effect of amines on functions of isolated neutrophils. / Thomas, Edwin; Grisham, M. B.; Jefferson, M. M.

In: Journal of Clinical Investigation, Vol. 72, No. 2, 01.01.1983, p. 441-454.

Research output: Contribution to journalArticle

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abstract = "Isolated neutrophilic leukocytes were incubated with primary amines and related nitrogenous compounds. Stimulation of neutrophil oxygen (O2) metabolism with phorbol myristate acetate or opsonized zymosan resulted in production of hydrogen peroxide (H2O2), myeloperoxidase-catalyzed oxidation of chloride (Cl-) to hypochlorous acid (HOCl), and the reaction of HOCl with the added compounds to yield nitrogen-chlorine (N-Cl) derivatives. Formation of N-Cl derivatives of low lipid solubility resulted in accumulation of the derivatives in the extracellular medium. These oxidizing agents were identified and measured on the basis of their absorption spectra and their ability to oxidize 5-thio-2-nitrobenzoic acid to the disulfide form. The yield of N-Cl derivatives was in the order: taurine > Tris > spermidine > spermine > glucosamine > putrescine > guanidinoacetate. Accumulation of N-Cl derivatives was also observed in the absence of added amines, owing to the reaction of HOCl with endogenous taurine and other amines that were released from the cells into the medium. In the presence of compounds that yield lipophilic N-Cl derivatives, little or no accumulation of oxidizing agents was observed. Instead, these compounds inhibited the accumulation of N-Cl derivatives that was obtained with taurine, and their effect was competitive with taurine. Inhibition was in the order: methylamine > ethanolamine > phenylethylamine > p-toluenesulfonamide > ammonia > guanidine. Formation of lipophilic N-Cl derivatives also resulted in inhibition of O2 uptake and glucose metabolism. Inhibition was prevented by adding catalase to eliminate H2O2, dapsone to inhibit myeloperoxidase, taurine to compete for reaction with HOCl, or compounds that are rapidly oxidized by HOCl or N-Cl derivatives, to reduce these oxidizing agents. The results indicate that: (a) formation of N-Cl derivatives that do not penetrate biological membranes can protect leukocytes against the cytotoxicity of HOCl and lipophilic N-Cl derivatives, and (b) formation of membrane-permeable N-Cl derivatives in the absence of target cells or readily oxidized substances results in oxidative attack by the N-Cl derivatives on leukocyte components and inhibition of leukocyte functions.",
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N2 - Isolated neutrophilic leukocytes were incubated with primary amines and related nitrogenous compounds. Stimulation of neutrophil oxygen (O2) metabolism with phorbol myristate acetate or opsonized zymosan resulted in production of hydrogen peroxide (H2O2), myeloperoxidase-catalyzed oxidation of chloride (Cl-) to hypochlorous acid (HOCl), and the reaction of HOCl with the added compounds to yield nitrogen-chlorine (N-Cl) derivatives. Formation of N-Cl derivatives of low lipid solubility resulted in accumulation of the derivatives in the extracellular medium. These oxidizing agents were identified and measured on the basis of their absorption spectra and their ability to oxidize 5-thio-2-nitrobenzoic acid to the disulfide form. The yield of N-Cl derivatives was in the order: taurine > Tris > spermidine > spermine > glucosamine > putrescine > guanidinoacetate. Accumulation of N-Cl derivatives was also observed in the absence of added amines, owing to the reaction of HOCl with endogenous taurine and other amines that were released from the cells into the medium. In the presence of compounds that yield lipophilic N-Cl derivatives, little or no accumulation of oxidizing agents was observed. Instead, these compounds inhibited the accumulation of N-Cl derivatives that was obtained with taurine, and their effect was competitive with taurine. Inhibition was in the order: methylamine > ethanolamine > phenylethylamine > p-toluenesulfonamide > ammonia > guanidine. Formation of lipophilic N-Cl derivatives also resulted in inhibition of O2 uptake and glucose metabolism. Inhibition was prevented by adding catalase to eliminate H2O2, dapsone to inhibit myeloperoxidase, taurine to compete for reaction with HOCl, or compounds that are rapidly oxidized by HOCl or N-Cl derivatives, to reduce these oxidizing agents. The results indicate that: (a) formation of N-Cl derivatives that do not penetrate biological membranes can protect leukocytes against the cytotoxicity of HOCl and lipophilic N-Cl derivatives, and (b) formation of membrane-permeable N-Cl derivatives in the absence of target cells or readily oxidized substances results in oxidative attack by the N-Cl derivatives on leukocyte components and inhibition of leukocyte functions.

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