The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages.

Journal Article

The antiapoptotic protein Mcl-1, a member of the Bcl-2 family, plays critical roles in promoting the survival of lymphocytes and hematopoietic stem cells. Although previous studies have implicated Mcl-1 in regulating the survival of neutrophils and macrophages, the in vivo function of Mcl-1 in these 2 cell lineages remained unclear. To address this, we have generated mice conditionally lacking Mcl-1 expression in neutrophils and macrophages. We show that Mcl-1 conditional knockout mice had a severe defect in neutrophil survival, whereas macrophage survival was normal. The granulocyte compartment in the blood, spleen, and bone marrow of Mcl-1 conditional knockout mice exhibited an approximately 2- to 3-fold higher apoptotic rate than control cells. In contrast, resting and activated macrophages from Mcl-1-deficient mice exhibited normal survival and contained up-regulated expression of Bcl-2 and Bcl-xL. These data suggest that Mcl-1 plays a nonredundant role in promoting the survival of neutrophils but not macrophages.

Full Text

Duke Authors

Cited Authors

  • Dzhagalov, I; St John, A; He, Y-W

Published Date

  • February 15, 2007

Published In

Volume / Issue

  • 109 / 4

Start / End Page

  • 1620 - 1626

PubMed ID

  • 17062731

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2006-03-013771

Language

  • eng

Conference Location

  • United States