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

Richter, J LU ; Gullberg, U LU and Lantz, M LU (1995) In Journal of Immunology 154(8). p.9-4142
Abstract

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... (More)

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.

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organization
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Contribution to journal
publication status
published
subject
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
in
Journal of Immunology
volume
154
issue
8
pages
8 pages
publisher
American Association of Immunologists
external identifiers
  • Scopus:0028968394
ISSN
0022-1767
language
English
LU publication?
yes
id
43ac15d3-b2f7-4966-ac64-7db855f93394
date added to LUP
2016-06-02 10:10:26
date last changed
2016-10-13 05:09:45
@misc{43ac15d3-b2f7-4966-ac64-7db855f93394,
  abstract     = {<p>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.</p>},
  author       = {Richter, J and Gullberg, U and Lantz, M},
  issn         = {0022-1767},
  keyword      = {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},
  language     = {eng},
  month        = {04},
  number       = {8},
  pages        = {9--4142},
  publisher    = {ARRAY(0x7b81918)},
  series       = {Journal of Immunology},
  title        = {TNF-induced superoxide anion production in adherent human neutrophils involves both the p55 and p75 TNF receptor},
  volume       = {154},
  year         = {1995},
}