The role of receptors for tumour necrosis factor-alpha in the induction of human polymorphonuclear neutrophil chemiluminescence.
Tumour necrosis factor-alpha (TNF-alpha) is a potent mediator of inflammation, which exerts profound effects on polymorphonuclear neutrophils (PMN). TNF-alpha binds to distinct cell surface receptors termed p55 and p75, expressed in approximately equal amounts on the PMN surface. We have studied the effects of TNF-alpha on the priming of F-Met-Leu-Phe (FMLP)-stimulated oxidative metabolism of PMN, using a luminol-enhanced chemiluminescence assay, and have examined the relative roles of PMN receptors for TNF-alpha in priming this oxidative metabolism, using antibodies with p55 and p75 receptor-specific agonistic and antagonistic activities. We have obtained the following results: (1) Antibody Htr-9 with agonistic activity at the p55 receptor mimicked the effect of TNF-alpha; however, a combination of Htr-9 and TNF-alpha did not results in any further increase in chemiluminescence relative to the response observed with TNF-alpha alone. The p75 agonistic antibody MR2-1 actually decreased basal and FMLP-enhanced chemiluminescence. Additionally, MR2-1 substantially inhibited the effects of both TNF-alpha itself and of the p55 agonist Htr-9. (2) Addition of antibodies with antagonistic activities at the p55 (antibody TBP-2) and p75 (antibody Utr-1) receptors resulted in a marked inhibition of the PMN response to TNF-alpha. A combination of both Utr-1 and TBP-2 was most effective at inhibiting the action of TNF. We have confirmed previously published observations that TNF-alpha alone effectively stimulates the oxidative metabolism of PMN in vitro, and that pre-incubation of PMN with TNF-alpha enhances subsequent generation of oxidative metabolites in response to FMLP. We conclude that both p55 and p75 receptors play a critical role in mediating the activation of PMN by TNF-alpha.
Zeman
K
K
Department of Clinical Immunology, Military Medical Academy, Lódź, Poland.
Kantorski
J
J
Paleolog
E M
EM
Feldmann
M
M
Tchórzewski
H
H
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry*; D008163:Luminescent Measurements; D008165:Luminol / Q000737:chemistry*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D016897:Respiratory Burst / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007202:Indicators and Reagents; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008165:Luminol