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Development and Identification of a Novel Subpopulation of Human Neutrophil-derived Giant Phagocytes In Vitro
Published on: January 25, 2017
Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function
Desiree A Steimer1, Kelli Boyd, Osamu Takeuchi
1Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Blood
|December 10, 2008
Summary
Myeloid cell leukemia-1 (MCL-1) is essential for neutrophil development but not monocyte development. MCL-1 antagonizes BIM in macrophages, preventing excessive death during bacterial infections.
Area of Science:
- Immunology
- Cell Biology
- Hematopoiesis
Background:
- Myeloid cell leukemia-1 (MCL-1) is a key regulator of cell survival during hematopoiesis.
- Its specific roles in myeloid cell differentiation, development, and effector functions remain incompletely understood.
Purpose of the Study:
- To investigate the selective roles of MCL-1 in myeloid cell development and function.
- To elucidate the mechanisms by which MCL-1 regulates neutrophil and monocyte/macrophage survival and effector responses.
Main Methods:
- Lineage-specific deletion of MCL-1 in myeloid precursors.
- Genetic deletion of proapoptotic factors (Bim, Puma, Bax, Bak) and cytokine treatment.
- Assessment of neutrophil and monocyte/macrophage development and survival during bacterial phagocytosis.
Main Results:
- MCL-1 deletion in myeloid precursors caused neutropenia due to death during differentiation, which was rescued by blocking intrinsic apoptosis (Bax/Bak deletion).
- Monocyte and macrophage development were unaffected by MCL-1 deletion.
- MCL-1-deficient macrophages showed increased death during bacterial phagocytosis, which was rescued by Bim deletion, suggesting MCL-1 antagonizes BIM.
Conclusions:
- MCL-1 is critically required for neutrophil development but not for monocyte/macrophage development.
- MCL-1 functions to antagonize BIM, thereby setting the threshold for apoptosis during macrophage effector responses to bacterial infection.
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