title: The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages.
abstract: 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.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Dzhagalov
authors.forename: Ashley
authors.initials: A
authors.lastname: St John
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics; D051020:bcl-X Protein / Q000235:genetics
chemical_list: C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein