TNF-induced superoxide anion production in adherent human neutrophils involves both the p55 and p75 TNF receptor
Författare
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.
Publiceringsår
1995-04-15
Språk
Engelska
Sidor
9-4142
Publikation/Tidskrift/Serie
Journal of Immunology
Volym
154
Issue
8
Dokumenttyp
Artikel i tidskrift
Förlag
American Association of Immunologists
Ämne
- Cell and Molecular Biology
Nyckelord
- 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/Övrigt
- ISSN: 0022-1767