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Effect of Tumor Necrosis Factor on the Generation of Chlorinated Oxidants by Adherent Human Neutrophils
Author(s) -
Test Samuel T.
Publication year - 1991
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.50.2.131
Subject(s) - respiratory burst , tumor necrosis factor alpha , chemotaxis , myeloperoxidase , superoxide , stimulation , necrosis , n formylmethionine leucyl phenylalanine , neutrophile , biology , medicine , immunology , endocrinology , biochemistry , inflammation , receptor , enzyme
Human neutrophils adherent to simulated biologic surfaces undergo significant activation of the respiratory burst over prolonged periods of time in response to stimulation with the cytokines tumor necrosis factor‐alpha (TNFα) or tumor necrosis factor‐beta (TNFβ) or with the chemotactic peptide N‐formyl‐methionylleucylphenylalanine (FMLP). In this study, neutrophils were examined for their ability to generate the highly reactive and powerful oxidant hypochlorous acid (HOCI) and the longer‐lived, less reactive endogenous nitrogen‐chlorine (N‐CI) derivatives in response to these stimuli either alone or when exposed to recombinant human TNFα (rTNFα) or β (rTNFβ) prior to addition of FMLP. Neutrophils adherent to fetal bovine serum‐coated polystyrene tissue culture wells were able to generate only small quantities of HOCI when incubated with rTNFα, rTNFβ, or FMLP individually. However, when neutrophils were first incubated with either rTNFα or rTNFβ prior to addition of FMLP, there was a marked increase in HOCI generation. Neutrophils stimulated in such a manner consumed ~18% of the HOCI generated in the formation of N‐CI derivatives. Further scrutiny of the response to the combination of rTNFα and FMLP revealed that HOCI release was rapid, with 80% of total HOCI accumulation occurring within 15 min after FMLP addition. The amount of HOCI generated was dependent on the number of cells added and on the concentration of both rTNFα and FMLP. Comparison of HOCI generation with superoxide anion and myeloperoxidase release showed that the amount of HOCI generated was limited primarily by the amount of myeloperoxidase released rather than by the degree of respiratory burst activation. These results demonstrate that human neutrophils stimulated with FMLP after a brief incubation with rTNFα or rTNFβ can generate cytotoxic and microbicidal concentrations of chlorinated oxidants.