TNF-induced superoxide anion production in adherent human neutrophils involves both the p55 and p75 TNF receptor
(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.
(Less)
- author
- Richter, J ; Gullberg, U LU and Lantz, M LU
- organization
- publishing date
- 1995-04-15
- type
- 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
-
- pmid:7706751
- scopus:14844353470
- 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
- 2024-01-04 07:57:32
@article{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}}, 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}}, language = {{eng}}, month = {{04}}, number = {{8}}, pages = {{9--4142}}, publisher = {{American Association of Immunologists}}, 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}}, }