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TNF-induced superoxide anion production in adherent human neutrophils involves both the p55 and p75 TNF receptor

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Author

Summary, in English

TNF, a potent activator of neutrophil granulocytes, acts via two cell-surface receptors: the p55-TNF receptor (TNF-R55) and the p75-TNF receptor (TNF-R75), which can be cleaved from the cell surface and thus form soluble TNF-binding proteins (TNF-BP). The role of the two receptors in activation of the neutrophil respiratory burst was investigated. Two mAbs reacting with TNF-R55 (H398 and TBP2) induced O2 release in a similar manner but to a lesser extent than TNF. TBP2, however, required preincubation at 4 degrees C to exert its effect. Preincubation of neutrophils (both at 4 and 37 degrees C) with mAb to TNF-R75 decreased TNF-induced superoxide anion production by 67 and 64%, respectively, indicating the essential role also for TNF-R75 in neutrophil activation. This inhibitory effect could not be explained by cross-down-regulation of TNF-R55 because the TNF-R75 mAb had no effect on TNF binding to TNF-R55 as determined by binding of 125I-labeled TNF or release of TNF-R55-BP as measured by ELISA. Furthermore, the TNF-R75 mAb did not decrease superoxide anion generation induced by the TNF-R55 mAb H398, thus ruling out that the inhibitory effect of the TNF-R75 mAb is due to inhibition of the signaling pathway downstream of TNF-R55. In contrast to the TNF-R75 mAb, TNF-R55 mAbs induced down-regulation of TNF-R75 and shedding of both TNF-R55-BP and TNF-R75-BP. We conclude that both TNF-R55 and TNF-R75 are involved in TNF-induced activation of the neutrophil respiratory burst.

Publishing year

1995-04-15

Language

English

Pages

9-4142

Publication/Series

Journal of Immunology

Volume

154

Issue

8

Document type

Journal article

Publisher

American Association of Immunologists

Topic

  • Cell and Molecular Biology

Keywords

  • Antibodies, Monoclonal
  • Carrier Proteins
  • Cell Adhesion
  • Down-Regulation
  • Humans
  • In Vitro Techniques
  • Molecular Weight
  • Neutrophil Activation
  • Neutrophils
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Respiratory Burst
  • Superoxides
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factor-alpha

Status

Published

ISBN/ISSN/Other

  • ISSN: 0022-1767