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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.

Original publication

DOI

10.1016/0165-2478(96)02613-2

Type

Journal article

Journal

Immunology letters

Publication Date

10/1996

Volume

53

Pages

45 - 50

Addresses

Department of Clinical Immunology, Military Medical Academy, Lódź, Poland.

Keywords

Neutrophils, Humans, Luminol, N-Formylmethionine Leucyl-Phenylalanine, Tumor Necrosis Factor-alpha, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, Recombinant Fusion Proteins, Antigens, CD, Antibodies, Monoclonal, Indicators and Reagents, Chemiluminescent Measurements, Respiratory Burst, Adult