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Soluble CD137 (4-1BB) ligand is released following leukocyte activation and is found in sera of patients with hematological malignancies.
J Immunol. 2001 Oct 01; 167(7):4059-66.JI

Abstract

Expression of CD137 ligand (4-1BBL), a member of the TNF family of proteins, has been reported on several types of APCs, various carcinoma cells, and can be induced on activated T cells. In this study, we report that the soluble ligand was released constitutively at low levels from leukocytes and at higher levels following cellular activation. Release from cells was blocked by addition of a metalloproteinase inhibitor which concomitantly caused the accumulation of 4-1BBL on the cell surface. In addition, we show that a soluble form of 4-1BBL was present at high levels in the sera of some patients with various hematological diseases, but only at low levels in healthy donors. Soluble 4-1BBL was active in that it competed with recombinant 4-1BBL for binding to the 4-1BB receptor and was able to costimulate IL-2 and IFN-gamma release from peripheral T cells. These results indicate that the release of soluble 4-1BBL from the cell surface is mediated by one or more sheddases and likely regulates 4-1BB-4-1BBL interactions between cells in vivo. Cleavage of 4-1BBL to an active soluble form would alter both proximal and distal cellular responses, including cell survival and costimulatory or inflammatory responses, that are mediated through the 4-1BB pathway. This, in turn, would likely alter disease progression or outcome.

Authors+Show Affiliations

Department of Immunology, Inflammation, and Pulmonary Diseases, Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, NJ 08540, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11564827

Citation

Salih, H R., et al. "Soluble CD137 (4-1BB) Ligand Is Released Following Leukocyte Activation and Is Found in Sera of Patients With Hematological Malignancies." Journal of Immunology (Baltimore, Md. : 1950), vol. 167, no. 7, 2001, pp. 4059-66.
Salih HR, Schmetzer HM, Burke C, et al. Soluble CD137 (4-1BB) ligand is released following leukocyte activation and is found in sera of patients with hematological malignancies. J Immunol. 2001;167(7):4059-66.
Salih, H. R., Schmetzer, H. M., Burke, C., Starling, G. C., Dunn, R., Pelka-Fleischer, R., Nuessler, V., & Kiener, P. A. (2001). Soluble CD137 (4-1BB) ligand is released following leukocyte activation and is found in sera of patients with hematological malignancies. Journal of Immunology (Baltimore, Md. : 1950), 167(7), 4059-66.
Salih HR, et al. Soluble CD137 (4-1BB) Ligand Is Released Following Leukocyte Activation and Is Found in Sera of Patients With Hematological Malignancies. J Immunol. 2001 Oct 1;167(7):4059-66. PubMed PMID: 11564827.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Soluble CD137 (4-1BB) ligand is released following leukocyte activation and is found in sera of patients with hematological malignancies. AU - Salih,H R, AU - Schmetzer,H M, AU - Burke,C, AU - Starling,G C, AU - Dunn,R, AU - Pelka-Fleischer,R, AU - Nuessler,V, AU - Kiener,P A, PY - 2001/9/21/pubmed PY - 2002/1/5/medline PY - 2001/9/21/entrez SP - 4059 EP - 66 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 167 IS - 7 N2 - Expression of CD137 ligand (4-1BBL), a member of the TNF family of proteins, has been reported on several types of APCs, various carcinoma cells, and can be induced on activated T cells. In this study, we report that the soluble ligand was released constitutively at low levels from leukocytes and at higher levels following cellular activation. Release from cells was blocked by addition of a metalloproteinase inhibitor which concomitantly caused the accumulation of 4-1BBL on the cell surface. In addition, we show that a soluble form of 4-1BBL was present at high levels in the sera of some patients with various hematological diseases, but only at low levels in healthy donors. Soluble 4-1BBL was active in that it competed with recombinant 4-1BBL for binding to the 4-1BB receptor and was able to costimulate IL-2 and IFN-gamma release from peripheral T cells. These results indicate that the release of soluble 4-1BBL from the cell surface is mediated by one or more sheddases and likely regulates 4-1BB-4-1BBL interactions between cells in vivo. Cleavage of 4-1BBL to an active soluble form would alter both proximal and distal cellular responses, including cell survival and costimulatory or inflammatory responses, that are mediated through the 4-1BB pathway. This, in turn, would likely alter disease progression or outcome. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/11564827/Soluble_CD137__4_1BB__ligand_is_released_following_leukocyte_activation_and_is_found_in_sera_of_patients_with_hematological_malignancies_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=11564827 DB - PRIME DP - Unbound Medicine ER -