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BCL-XL antagonism selectively reduces neutrophil life span within inflamed tissues without causing neutropenia.
Carrington, Emma M; Louis, Cynthia; Kratina, Tobias; Hancock, Manuela; Keenan, Christine R; Iannarella, Nadia; Allan, Rhys S; Wardak, Ahmad Z; Czabotar, Peter E; Herold, Marco J; Schenk, Robyn L; White, Christine A; D'Silva, Damian; Yang, Yuyan; Wong, Wesley; Wong, Huon; Bryant, Vanessa L; Huntington, Nicholas D; Rautela, Jai; Sutherland, Robyn M; Zhan, Yifan; Hansen, Jacinta; Nhu, Duong; Lessene, Guillaume; Wicks, Ian P; Lew, Andrew M.
Afiliación
  • Carrington EM; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Louis C; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Kratina T; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Hancock M; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Keenan CR; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Iannarella N; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Allan RS; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Wardak AZ; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Czabotar PE; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Herold MJ; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Schenk RL; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • White CA; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • D'Silva D; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Yang Y; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Wong W; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Wong H; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Bryant VL; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Huntington ND; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Rautela J; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Sutherland RM; Department of Medical Biology, University of Melbourne, Parkville, Australia.
  • Zhan Y; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Hansen J; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Nhu D; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Lessene G; Royal Melbourne Hospital, Parkville, Australia.
  • Wicks IP; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Lew AM; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Blood Adv ; 5(11): 2550-2562, 2021 06 08.
Article en En | MEDLINE | ID: mdl-34100903
ABSTRACT
Neutrophils help to clear pathogens and cellular debris, but can also cause collateral damage within inflamed tissues. Prolonged neutrophil residency within an inflammatory niche can exacerbate tissue pathology. Using both genetic and pharmacological approaches, we show that BCL-XL is required for the persistence of neutrophils within inflammatory sites in mice. We demonstrate that a selective BCL-XL inhibitor (A-1331852) has therapeutic potential by causing apoptosis in inflammatory human neutrophils ex vivo. Moreover, in murine models of acute and chronic inflammatory disease, it reduced inflammatory neutrophil numbers and ameliorated tissue pathology. In contrast, there was minimal effect on circulating neutrophils. Thus, we show a differential survival requirement in activated neutrophils for BCL-XL and reveal a new therapeutic approach to neutrophil-mediated diseases.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neutropenia / Neutrófilos Límite: Animals Idioma: En Revista: Blood Adv Año: 2021 Tipo del documento: Article País de afiliación: Australia
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neutropenia / Neutrófilos Límite: Animals Idioma: En Revista: Blood Adv Año: 2021 Tipo del documento: Article País de afiliación: Australia