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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1620-1626.
Prepublished online as a Blood First Edition Paper on October 24, 2006; DOI 10.1182/blood-2006-03-013771.
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IMMUNOBIOLOGY
The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages
Ivan Dzhagalov1,
Ashley St. John1, and
You-Wen He1
1 Department of Immunology, Duke University Medical Center, Durham, NC
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.
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