The BH3-mimetic ABT-737 induces mast cell apoptosis in vitro and in vivo: potential for therapeutics

The Journal of Immunology : Official Journal of the American Association of Immunologists
Mats KarlbergG Nilsson

Abstract

Mast cells and their mediators are implicated in the pathogenesis of many different diseases. One possible therapeutic intervention in mast cell-associated diseases can be to reduce the number of tissue mast cells by inducing mast cell apoptosis. In this study, we demonstrate that mast cells exhibit a high sensitivity to ABT-737, a BH3-only mimetic molecule that induces apoptosis through high-affinity binding to the prosurvival proteins, Bcl-2, Bcl-XL, and Bcl-w. Primary mast cells as well as mast cell lines tested succumbed to apoptosis in response to the inhibitor at varying but seemingly low concentrations compared with other leukocytes investigated. I.p. injections of ABT-737 in mice resulted in a total abolishment of mast cells in the peritoneum. Confocal microscopy analysis of peritoneal cells revealed apoptotic bodies of mast cells being phagocytosed by macrophages. In addition, ex vivo treatment of human skin biopsies with ABT-737 demonstrated increased mast cell apoptosis. The data we present in this article show exceptional mast cell sensitivity to ABT-737, a selective inhibitor of antiapoptotic proteins, rendering a possible application for BH3-only mimetic compounds like ABT-737 in mast cell-associated diseases, suc...Continue Reading

References

Jun 14, 2001·Journal of Clinical Immunology·Y A MekoriD D Metcalfe
Jul 3, 2002·Nature Reviews. Immunology·Richard M Pope
Dec 20, 2002·Nature·Carl Nathan
Dec 20, 2002·Nature·Christophe Benoist, Diane Mathis
Mar 13, 2003·Experimental Dermatology·Petri K KivinenIlkka T Harvima
Aug 26, 2003·The American Journal of Pathology·Karin HartmannBeate M Henz
Oct 2, 2004·Nature Reviews. Immunology·Jean S Marshall
May 20, 2005·Nature·Tilman OltersdorfSaul H Rosenberg
Oct 4, 2005·The Journal of Clinical Investigation·Anthony Letai
Dec 22, 2005·Nature Immunology·Charles N Serhan, John Savill
Jan 6, 2007·Cell Death and Differentiation·H ZhangC Tse
Mar 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria EkoffGunnar Nilsson
Mar 27, 2007·Cell·Kylie D MasonBenjamin T Kile
Apr 3, 2007·Trends in Immunology·Martin Metz, Marcus Maurer
Apr 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ramzi M MohammadAyad Al-Katib
May 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Odile MalbecMarc Daëron
Jun 5, 2007·Nature Medicine·Jiusong SunGuo-Ping Shi
Aug 4, 2007·Science·Mitch Leslie
Dec 7, 2007·Blood·Victoria Del Gaizo MooreAnthony Letai
Dec 22, 2007·Nature Reviews. Molecular Cell Biology·Richard J Youle, Andreas Strasser
Apr 15, 2008·Trends in Pharmacological Sciences·John M HallettAdriano G Rossi
May 3, 2008·Cancer Research·Christin TseSteven W Elmore
May 17, 2008·Nature Reviews. Immunology·Stephen J GalliMindy Tsai
Aug 8, 2008·Blood·Dean D Metcalfe
Aug 23, 2008·Archives of Dermatological Research·Ilkka T HarvimaAnita Naukkarinen
Nov 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kylie D MasonAndrew W Roberts
Dec 2, 2008·Nature Reviews. Drug Discovery·Guillaume LessenePeter M Colman
Apr 4, 2009·Nature Reviews. Cancer·Mark S CraggClare L Scott
Jun 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Philip D BardwellTariq Ghayur

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Citations

Jul 2, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jun-Xia WangPeter A Nigrovic
Jan 22, 2013·Communicative & Integrative Biology·Qiang Liu, Hong-Gang Wang
Sep 30, 2017·Cell Death and Differentiation·Ramona ReinhartThomas Kaufmann
May 2, 2016·Naunyn-Schmiedeberg's Archives of Pharmacology·Gerhard J MolderingsLawrence B Afrin
Mar 27, 2015·Experimental Dermatology·Eva HagforsenGunnar Pejler
May 28, 2011·Transplant International : Official Journal of the European Society for Organ Transplantation·Pietro E CippàThomas Fehr
Jun 11, 2016·Experimental and Therapeutic Medicine·Haiyan GaoFeng Liu
Jun 8, 2011·Scandinavian Journal of Immunology·F R MeloG Pejler
Dec 2, 2017·Clinical and Experimental Pharmacology & Physiology·Na-Ra HanHyun-Ja Jeong
Apr 21, 2020·Trends in Cell Biology·Stephen Jun Fei ChongShazib Pervaiz
Jan 1, 2018·Cell Death and Differentiation·Ramona ReinhartThomas Kaufmann
Apr 29, 2014·The Journal of Allergy and Clinical Immunology·Ilkka T HarvimaMarcus Maurer

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