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CD137 activation abrogates granulocyte-macrophage colony-stimulating factor-mediated anti-apoptosis in neutrophils.
Eur J Immunol. 2000 Dec; 30(12):3441-6.EJ

Abstract

CD137 (ILA / 4-1BB) is a member of the TNF / NGF receptor family, and has previously been suggested to be involved in T cell activation and differentiation. Here, we demonstrate that blood neutrophils from control individuals and patients with cystic fibrosis express CD137 mRNA and surface protein. In contrast, lung neutrophils derived from patients with cystic fibrosis did not express detectable CD137 levels. Such CD137-deficient neutrophils could also be generated from normal neutrophils by TNF-alpha stimulation in vitro. TNF-alpha was found to be highly expressed in epithelial cells from cystic fibrosis but not normal lungs, suggesting that TNF-alpha might account for reduced neutrophil CD137 levels under inflammatory conditions in vivo. To investigate whether CD137 is involved in the regulation of apoptosis, neutrophils were activated with functional anti-CD137 antibody in the presence or absence of different neutrophil survival factors in vitro. Activation of CD137 abrogated GM-CSF-mediated anti-apoptosis in normal but not in CD137-deficient neutrophils. Moreover, G-CSF- and IFN-gamma-mediated neutrophil anti-apoptosis was not affected by anti-CD137 antibody treatment. In conclusion, these data suggest that CD137 activation may limit GM-CSF-mediated anti-apoptosis of neutrophils. The absence of this anti-inflammatory mechanism in inflammatory responses might be associated with massive neutrophil accumulation and consequent tissue damage.

Authors+Show Affiliations

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.No 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

11093162

Citation

Heinisch, I V., et al. "CD137 Activation Abrogates Granulocyte-macrophage Colony-stimulating Factor-mediated Anti-apoptosis in Neutrophils." European Journal of Immunology, vol. 30, no. 12, 2000, pp. 3441-6.
Heinisch IV, Daigle I, Knöpfli B, et al. CD137 activation abrogates granulocyte-macrophage colony-stimulating factor-mediated anti-apoptosis in neutrophils. Eur J Immunol. 2000;30(12):3441-6.
Heinisch, I. V., Daigle, I., Knöpfli, B., & Simon, H. U. (2000). CD137 activation abrogates granulocyte-macrophage colony-stimulating factor-mediated anti-apoptosis in neutrophils. European Journal of Immunology, 30(12), 3441-6.
Heinisch IV, et al. CD137 Activation Abrogates Granulocyte-macrophage Colony-stimulating Factor-mediated Anti-apoptosis in Neutrophils. Eur J Immunol. 2000;30(12):3441-6. PubMed PMID: 11093162.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD137 activation abrogates granulocyte-macrophage colony-stimulating factor-mediated anti-apoptosis in neutrophils. AU - Heinisch,I V, AU - Daigle,I, AU - Knöpfli,B, AU - Simon,H U, PY - 2000/11/28/pubmed PY - 2001/2/28/medline PY - 2000/11/28/entrez SP - 3441 EP - 6 JF - European journal of immunology JO - Eur J Immunol VL - 30 IS - 12 N2 - CD137 (ILA / 4-1BB) is a member of the TNF / NGF receptor family, and has previously been suggested to be involved in T cell activation and differentiation. Here, we demonstrate that blood neutrophils from control individuals and patients with cystic fibrosis express CD137 mRNA and surface protein. In contrast, lung neutrophils derived from patients with cystic fibrosis did not express detectable CD137 levels. Such CD137-deficient neutrophils could also be generated from normal neutrophils by TNF-alpha stimulation in vitro. TNF-alpha was found to be highly expressed in epithelial cells from cystic fibrosis but not normal lungs, suggesting that TNF-alpha might account for reduced neutrophil CD137 levels under inflammatory conditions in vivo. To investigate whether CD137 is involved in the regulation of apoptosis, neutrophils were activated with functional anti-CD137 antibody in the presence or absence of different neutrophil survival factors in vitro. Activation of CD137 abrogated GM-CSF-mediated anti-apoptosis in normal but not in CD137-deficient neutrophils. Moreover, G-CSF- and IFN-gamma-mediated neutrophil anti-apoptosis was not affected by anti-CD137 antibody treatment. In conclusion, these data suggest that CD137 activation may limit GM-CSF-mediated anti-apoptosis of neutrophils. The absence of this anti-inflammatory mechanism in inflammatory responses might be associated with massive neutrophil accumulation and consequent tissue damage. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/11093162/CD137_activation_abrogates_granulocyte_macrophage_colony_stimulating_factor_mediated_anti_apoptosis_in_neutrophils_ L2 - https://doi.org/10.1002/1521-4141(2000012)30:12<3441::AID-IMMU3441>3.0.CO;2-L DB - PRIME DP - Unbound Medicine ER -