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

Blood. 2007 Feb 15;109(4):1620-6. doi: 10.1182/blood-2006-03-013771. Epub 2006 Oct 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Survival*
  • Macrophages / cytology*
  • Mice
  • Mice, Knockout
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / physiology*
  • Neutrophils / cytology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Up-Regulation / genetics
  • bcl-X Protein / genetics


  • Mcl1 protein, mouse
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein