TR60 and TR80 tumor necrosis factor (TNF)-receptors can independently mediate cytolysis - PubMed (original) (raw)
Affiliations
- PMID: 8394147
TR60 and TR80 tumor necrosis factor (TNF)-receptors can independently mediate cytolysis
M Grell et al. Lymphokine Cytokine Res. 1993 Jun.
Abstract
The human rhabdomyosarcoma cell line KYM-1 coexpresses high numbers of both tumor necrosis factor-alpha (TNF) receptors, TR60 and TR80, and is highly sensitive to TNF-induced cytotoxicity. We show here that each receptor type can mediate cytotoxicity on its own on selective stimulation. This was achieved using receptor specific antibodies, able to compete with ligand binding to the respective receptor molecules. Thus, the TR60-specific monoclonal antibody H398 was strongly agonistic, i.e., cytotoxic, in the presence of a secondary cross-linking immunoglobulin. Selective stimulation of TR80 by antibody-mediated receptor crosslinking also induced strong cytotoxicity in KYM-1 cells. Interestingly, when both receptor subsets were stimulated in parallel by limited receptor cross-linking, additive cytolytic effects were observed. In each case the respective Fab fragments showed no agonistic activity. When the natural ligand TNF was used to induce cytolysis, blocking studies with receptor specific Fab fragments indicated that the main cytotoxic effect of TNF is mediated via TR60, although these receptors represent only about 8% of the total TNF receptor number.
Similar articles
- TNF receptors TR60 and TR80 can mediate apoptosis via induction of distinct signal pathways.
Grell M, Zimmermann G, Hülser D, Pfizenmaier K, Scheurich P. Grell M, et al. J Immunol. 1994 Sep 1;153(5):1963-72. J Immunol. 1994. PMID: 8051401 - The TNF receptor in TNF-mediated cytotoxicity.
Kull FC Jr. Kull FC Jr. Nat Immun Cell Growth Regul. 1988;7(5-6):254-65. Nat Immun Cell Growth Regul. 1988. PMID: 2851740 Review. - Soluble and cell surface receptors for tumor necrosis factor.
Wallach D, Engelmann H, Nophar Y, Aderka D, Kemper O, Hornik V, Holtmann H, Brakebusch C. Wallach D, et al. Agents Actions Suppl. 1991;35:51-7. Agents Actions Suppl. 1991. PMID: 1664189 Review.
Cited by
- A conformation-selective monoclonal antibody against a small molecule-stabilised signalling-deficient form of TNF.
Lightwood DJ, Munro RJ, Porter J, McMillan D, Carrington B, Turner A, Scott-Tucker A, Hickford ES, Schmidt A, Fox D 3rd, Maloney A, Ceska T, Bourne T, O'Connell J, Lawson ADG. Lightwood DJ, et al. Nat Commun. 2021 Jan 25;12(1):583. doi: 10.1038/s41467-020-20825-6. Nat Commun. 2021. PMID: 33495445 Free PMC article. - Structural insights into the disruption of TNF-TNFR1 signalling by small molecules stabilising a distorted TNF.
McMillan D, Martinez-Fleites C, Porter J, Fox D 3rd, Davis R, Mori P, Ceska T, Carrington B, Lawson A, Bourne T, O'Connell J. McMillan D, et al. Nat Commun. 2021 Jan 25;12(1):582. doi: 10.1038/s41467-020-20828-3. Nat Commun. 2021. PMID: 33495441 Free PMC article. - A New Venue of TNF Targeting.
Steeland S, Libert C, Vandenbroucke RE. Steeland S, et al. Int J Mol Sci. 2018 May 11;19(5):1442. doi: 10.3390/ijms19051442. Int J Mol Sci. 2018. PMID: 29751683 Free PMC article. Review. - The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions.
Zhang T, Song X, Xu L, Ma J, Zhang Y, Gong W, Zhang Y, Zhou X, Wang Z, Wang Y, Shi Y, Bai H, Liu N, Yang X, Cui X, Cao Y, Liu Q, Song J, Li Y, Tang Z, Guo M, Wang L, Li K. Zhang T, et al. Cancer Immunol Immunother. 2018 Jul;67(7):1079-1090. doi: 10.1007/s00262-018-2160-x. Epub 2018 Apr 23. Cancer Immunol Immunother. 2018. PMID: 29687231 Free PMC article. - Novel strategies to mimic transmembrane tumor necrosis factor-dependent activation of tumor necrosis factor receptor 2.
Fischer R, Marsal J, Guttà C, Eisler SA, Peters N, Bethea JR, Pfizenmaier K, Kontermann RE. Fischer R, et al. Sci Rep. 2017 Jul 26;7(1):6607. doi: 10.1038/s41598-017-06993-4. Sci Rep. 2017. PMID: 28747780 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources