Immunomodulation by neutrophil myeloperoxidase and hydrogen peroxide

Differential susceptibility of human lymphocyte functions

A. El-Hag, P. E. Lipsky, M. Bennett, Robert A Clark

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

To coexistence of activated polymorphonuclear leukocytes and lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. To test this hypothesis, we examined the effects of neutrophil myeloperoxidase and H2O2 on lymphocytes. Human peripheral blood mononuclear leukocytes were exposed to myeloperoxidase, and H2O2-generating system (glucose + glucose oxidase), and a halide, and were then tested for functional activities. Natural killer activity against K562 cells, lymphocyte proliferation in response to mitogens, and generation of immunoglobulin-secreting cells were all susceptible to oxidative injury by myeloperoxidase and H2O2. The degree as well as the mechanism of suppression was dependent on the glucose oxidase concentration (i.e., the rate of H2O2 delivery). At low H2O2 flux, myeloperoxidase was essential for induction of lymphocyte suppression; as the rate of H2O2 generation increased, suppression became myeloperoxidase-independent and was mediated by H2O2 alone. Various lymphocyte functions were differentially susceptible to oxidative injury by myeloperoxidase and H2O2. The proliferative response to pokeweed mitogen was the least sensitive, whereas antibody formation was the most sensitive. Proliferative responses to concanavalin A and phytohemagglutinin as well as natural killer activity displayed intermediates degrees of susceptibility. In all assays, lymphocyte viability was >90%. Removal of monocytes from mononuclear leukocytes by adherence to glass increased susceptibility of lymphocytes to oxidative injury. Monocytes in proportions within the range present in peripheral blood mononuclear leukocytes protected lymphocytes functions against oxidative injury by myeloperoxidase and H2O2. This study demonstrates a differential susceptibility of various immune functions to oxidative injury by the neutrophil products myeloperoxidase and H2O2, and shows, in addition, that monocytes can modulate these interactions.

Original languageEnglish (US)
Pages (from-to)3420-3426
Number of pages7
JournalJournal of Immunology
Volume136
Issue number9
StatePublished - 1986
Externally publishedYes

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Immunomodulation
Hydrogen Peroxide
Peroxidase
Neutrophils
Lymphocytes
Mononuclear Leukocytes
Wounds and Injuries
Monocytes
Glucose Oxidase
Antibody-Producing Cells
Pokeweed Mitogens
K562 Cells
Phytohemagglutinins
Concanavalin A
Mitogens
Antibody Formation
Glass
Cell Proliferation
Glucose

ASJC Scopus subject areas

  • Immunology

Cite this

Immunomodulation by neutrophil myeloperoxidase and hydrogen peroxide : Differential susceptibility of human lymphocyte functions. / El-Hag, A.; Lipsky, P. E.; Bennett, M.; Clark, Robert A.

In: Journal of Immunology, Vol. 136, No. 9, 1986, p. 3420-3426.

Research output: Contribution to journalArticle

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abstract = "To coexistence of activated polymorphonuclear leukocytes and lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. To test this hypothesis, we examined the effects of neutrophil myeloperoxidase and H2O2 on lymphocytes. Human peripheral blood mononuclear leukocytes were exposed to myeloperoxidase, and H2O2-generating system (glucose + glucose oxidase), and a halide, and were then tested for functional activities. Natural killer activity against K562 cells, lymphocyte proliferation in response to mitogens, and generation of immunoglobulin-secreting cells were all susceptible to oxidative injury by myeloperoxidase and H2O2. The degree as well as the mechanism of suppression was dependent on the glucose oxidase concentration (i.e., the rate of H2O2 delivery). At low H2O2 flux, myeloperoxidase was essential for induction of lymphocyte suppression; as the rate of H2O2 generation increased, suppression became myeloperoxidase-independent and was mediated by H2O2 alone. Various lymphocyte functions were differentially susceptible to oxidative injury by myeloperoxidase and H2O2. The proliferative response to pokeweed mitogen was the least sensitive, whereas antibody formation was the most sensitive. Proliferative responses to concanavalin A and phytohemagglutinin as well as natural killer activity displayed intermediates degrees of susceptibility. In all assays, lymphocyte viability was >90{\%}. Removal of monocytes from mononuclear leukocytes by adherence to glass increased susceptibility of lymphocytes to oxidative injury. Monocytes in proportions within the range present in peripheral blood mononuclear leukocytes protected lymphocytes functions against oxidative injury by myeloperoxidase and H2O2. This study demonstrates a differential susceptibility of various immune functions to oxidative injury by the neutrophil products myeloperoxidase and H2O2, and shows, in addition, that monocytes can modulate these interactions.",
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