Poly-l-arginine and an N-formylated chemotactic peptide act synergistically with lectins and calcium ionophore to induce intense chemiluminescence and superoxide production in human blood leukocytes - Modulation by metabolic inhibitors, sugars, and polyelectrolytes

Isaac Ginsburg, Ruth Borinski, Meir Lahav, Yaacov Matzner, Ingvar Eliasson, Poul Christensen, Daniel Malamud

Research output: Contribution to journalArticle

Abstract

Various cationic polyelectrolytes (poly-α-amino acids and histones), lectins, the chemotactic peptide, f-methionyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187, and phorbol myristate acetate (PMA) were investigated regarding their capacity to induce luminol-dependent chemiluminescence (LDCL) and superoxide production by human blood leukocytes. Although when tested individually, poly-l-arginine (PARG), phytohemagglutinin (PHA), concanavalin A (Con A), or fMLP induced only a low to moderate LDCL response, very intense synergistic CL reactions were obtained by mixtures of PARG + PHA, PARG + Con A, PARG + PHA + fMLP, Ca2 + ionophore + PARG + PHA + fMLP, and PARG + PMA. The sequence of addition of the various agents to WBC in the presence of luminol absolutely determined the intensity of the LDCL signals obtained, the highest reactions being achieved when the WBC were preincubated for 2-3 rain with A23187 followed by the sequential addition of fMLP, PARG, and PHA. These "multiple hits" induced CL reactions which were many times higher than those obtained by each factor alone. On the other hand, neither poly-L-lysine, poly-L-ornithine, poly-L-histidine, nor poly-L-asparagine, when employed at equimolar concentrations, cooperated efficiently with PHA and fMLP to trigger synergistic LDCL response s in leukocytes. Concomitantly with the induction of LDCL, certain ligand mixtures also triggered the production of superoxide. The LDCL which was induced by the "cocktail" of agents was markedly inhibited by sodium azide (93% inhibition), but to a lesser extent by catalase (10% inhibition) or by snperoxide dismutase (20%-60% inhibition). On the other hand, scavengers of singlet oxygen and OH' (sodium benzoate, histidine) did not affect the synergistic LDCL responses induced by these multiple ligands. Cytochalasin B also markedly inhibited the LDCL responses induced either by soluble stimuli or by streptococci preopsonized either with histone or with polyanethole sulfonate. The LDCL responses which were induced by mixtures of PARG and concanavalin A were also strongly inhibited by mannose, a-methyl mannoside, and poly-L-glutamic acid: The data suggest that the LDCL responses induced by the soluble ligands involved a myeloperoxidase-catalyzed reaction. The possible employment of "cocktails" of ligands to enhance the bactericidal effects of PMNs, macrophages, and natural killer cells on microbial cells and mammalian targets is discussed.

Original languageEnglish (US)
Pages (from-to)1-26
Number of pages26
JournalInflammation
Volume8
Issue number1
DOIs
StatePublished - Mar 1984

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N-Formylmethionine Leucyl-Phenylalanine
Luminol
Calcium Ionophores
Luminescence
Lectins
Superoxides
Arginine
Leukocytes
methionyl-leucyl-phenylalanine
Phytohemagglutinins
Concanavalin A
Ligands
Calcimycin
Tetradecanoylphorbol Acetate
Histones
Polyelectrolytes
Sodium Benzoate
Sodium Azide
Singlet Oxygen
Cytochalasin B

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology
  • Cell Biology

Cite this

@article{2371c91cd803462599e8e0b3c3f970f2,
title = "Poly-l-arginine and an N-formylated chemotactic peptide act synergistically with lectins and calcium ionophore to induce intense chemiluminescence and superoxide production in human blood leukocytes - Modulation by metabolic inhibitors, sugars, and polyelectrolytes",
abstract = "Various cationic polyelectrolytes (poly-α-amino acids and histones), lectins, the chemotactic peptide, f-methionyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187, and phorbol myristate acetate (PMA) were investigated regarding their capacity to induce luminol-dependent chemiluminescence (LDCL) and superoxide production by human blood leukocytes. Although when tested individually, poly-l-arginine (PARG), phytohemagglutinin (PHA), concanavalin A (Con A), or fMLP induced only a low to moderate LDCL response, very intense synergistic CL reactions were obtained by mixtures of PARG + PHA, PARG + Con A, PARG + PHA + fMLP, Ca2 + ionophore + PARG + PHA + fMLP, and PARG + PMA. The sequence of addition of the various agents to WBC in the presence of luminol absolutely determined the intensity of the LDCL signals obtained, the highest reactions being achieved when the WBC were preincubated for 2-3 rain with A23187 followed by the sequential addition of fMLP, PARG, and PHA. These {"}multiple hits{"} induced CL reactions which were many times higher than those obtained by each factor alone. On the other hand, neither poly-L-lysine, poly-L-ornithine, poly-L-histidine, nor poly-L-asparagine, when employed at equimolar concentrations, cooperated efficiently with PHA and fMLP to trigger synergistic LDCL response s in leukocytes. Concomitantly with the induction of LDCL, certain ligand mixtures also triggered the production of superoxide. The LDCL which was induced by the {"}cocktail{"} of agents was markedly inhibited by sodium azide (93{\%} inhibition), but to a lesser extent by catalase (10{\%} inhibition) or by snperoxide dismutase (20{\%}-60{\%} inhibition). On the other hand, scavengers of singlet oxygen and OH' (sodium benzoate, histidine) did not affect the synergistic LDCL responses induced by these multiple ligands. Cytochalasin B also markedly inhibited the LDCL responses induced either by soluble stimuli or by streptococci preopsonized either with histone or with polyanethole sulfonate. The LDCL responses which were induced by mixtures of PARG and concanavalin A were also strongly inhibited by mannose, a-methyl mannoside, and poly-L-glutamic acid: The data suggest that the LDCL responses induced by the soluble ligands involved a myeloperoxidase-catalyzed reaction. The possible employment of {"}cocktails{"} of ligands to enhance the bactericidal effects of PMNs, macrophages, and natural killer cells on microbial cells and mammalian targets is discussed.",
author = "Isaac Ginsburg and Ruth Borinski and Meir Lahav and Yaacov Matzner and Ingvar Eliasson and Poul Christensen and Daniel Malamud",
year = "1984",
month = "3",
doi = "10.1007/BF00918349",
language = "English (US)",
volume = "8",
pages = "1--26",
journal = "Inflammation",
issn = "0360-3997",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Poly-l-arginine and an N-formylated chemotactic peptide act synergistically with lectins and calcium ionophore to induce intense chemiluminescence and superoxide production in human blood leukocytes - Modulation by metabolic inhibitors, sugars, and polyelectrolytes

AU - Ginsburg, Isaac

AU - Borinski, Ruth

AU - Lahav, Meir

AU - Matzner, Yaacov

AU - Eliasson, Ingvar

AU - Christensen, Poul

AU - Malamud, Daniel

PY - 1984/3

Y1 - 1984/3

N2 - Various cationic polyelectrolytes (poly-α-amino acids and histones), lectins, the chemotactic peptide, f-methionyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187, and phorbol myristate acetate (PMA) were investigated regarding their capacity to induce luminol-dependent chemiluminescence (LDCL) and superoxide production by human blood leukocytes. Although when tested individually, poly-l-arginine (PARG), phytohemagglutinin (PHA), concanavalin A (Con A), or fMLP induced only a low to moderate LDCL response, very intense synergistic CL reactions were obtained by mixtures of PARG + PHA, PARG + Con A, PARG + PHA + fMLP, Ca2 + ionophore + PARG + PHA + fMLP, and PARG + PMA. The sequence of addition of the various agents to WBC in the presence of luminol absolutely determined the intensity of the LDCL signals obtained, the highest reactions being achieved when the WBC were preincubated for 2-3 rain with A23187 followed by the sequential addition of fMLP, PARG, and PHA. These "multiple hits" induced CL reactions which were many times higher than those obtained by each factor alone. On the other hand, neither poly-L-lysine, poly-L-ornithine, poly-L-histidine, nor poly-L-asparagine, when employed at equimolar concentrations, cooperated efficiently with PHA and fMLP to trigger synergistic LDCL response s in leukocytes. Concomitantly with the induction of LDCL, certain ligand mixtures also triggered the production of superoxide. The LDCL which was induced by the "cocktail" of agents was markedly inhibited by sodium azide (93% inhibition), but to a lesser extent by catalase (10% inhibition) or by snperoxide dismutase (20%-60% inhibition). On the other hand, scavengers of singlet oxygen and OH' (sodium benzoate, histidine) did not affect the synergistic LDCL responses induced by these multiple ligands. Cytochalasin B also markedly inhibited the LDCL responses induced either by soluble stimuli or by streptococci preopsonized either with histone or with polyanethole sulfonate. The LDCL responses which were induced by mixtures of PARG and concanavalin A were also strongly inhibited by mannose, a-methyl mannoside, and poly-L-glutamic acid: The data suggest that the LDCL responses induced by the soluble ligands involved a myeloperoxidase-catalyzed reaction. The possible employment of "cocktails" of ligands to enhance the bactericidal effects of PMNs, macrophages, and natural killer cells on microbial cells and mammalian targets is discussed.

AB - Various cationic polyelectrolytes (poly-α-amino acids and histones), lectins, the chemotactic peptide, f-methionyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187, and phorbol myristate acetate (PMA) were investigated regarding their capacity to induce luminol-dependent chemiluminescence (LDCL) and superoxide production by human blood leukocytes. Although when tested individually, poly-l-arginine (PARG), phytohemagglutinin (PHA), concanavalin A (Con A), or fMLP induced only a low to moderate LDCL response, very intense synergistic CL reactions were obtained by mixtures of PARG + PHA, PARG + Con A, PARG + PHA + fMLP, Ca2 + ionophore + PARG + PHA + fMLP, and PARG + PMA. The sequence of addition of the various agents to WBC in the presence of luminol absolutely determined the intensity of the LDCL signals obtained, the highest reactions being achieved when the WBC were preincubated for 2-3 rain with A23187 followed by the sequential addition of fMLP, PARG, and PHA. These "multiple hits" induced CL reactions which were many times higher than those obtained by each factor alone. On the other hand, neither poly-L-lysine, poly-L-ornithine, poly-L-histidine, nor poly-L-asparagine, when employed at equimolar concentrations, cooperated efficiently with PHA and fMLP to trigger synergistic LDCL response s in leukocytes. Concomitantly with the induction of LDCL, certain ligand mixtures also triggered the production of superoxide. The LDCL which was induced by the "cocktail" of agents was markedly inhibited by sodium azide (93% inhibition), but to a lesser extent by catalase (10% inhibition) or by snperoxide dismutase (20%-60% inhibition). On the other hand, scavengers of singlet oxygen and OH' (sodium benzoate, histidine) did not affect the synergistic LDCL responses induced by these multiple ligands. Cytochalasin B also markedly inhibited the LDCL responses induced either by soluble stimuli or by streptococci preopsonized either with histone or with polyanethole sulfonate. The LDCL responses which were induced by mixtures of PARG and concanavalin A were also strongly inhibited by mannose, a-methyl mannoside, and poly-L-glutamic acid: The data suggest that the LDCL responses induced by the soluble ligands involved a myeloperoxidase-catalyzed reaction. The possible employment of "cocktails" of ligands to enhance the bactericidal effects of PMNs, macrophages, and natural killer cells on microbial cells and mammalian targets is discussed.

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