40.8:
Differentiation of Common Myeloid Progenitor Cells
Common myeloid progenitors or CMPs undergo multiple cell divisions before differentiating into granulocytes or phagocytes .
In response to an allergy or an infection, endothelial cells and fibroblasts release inflammatory cytokines called colony-stimulating factors or CSFs into the bloodstream.
At least four different types of CSFs participate in distinct combinations to help the progenitors divide and commit to specific cell types.
For example, during parasitic infection, interleukin 3 and GM CSF help CMPs differentiate into eosinophils that digest the parasite.
In contrast, granulocyte-CSF and macrophage-CSF released in response to a bacterial infection produce neutrophils and monocytes. Monocytes mature into macrophages, which along with neutrophils, phagocytose the invading bacteria.
Once the infection is cleared and CSF concentration drops, neutrophils die by apoptosis within a few days, while the macrophages continue to survive for months, circulating in the blood.
40.8:
Differentiation of Common Myeloid Progenitor Cells
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust immune system. In addition, during an injury or infection, many of these immune cells are lost in the action of immune defense. The adjoining endothelial cells of injured tissues, existing immune cells, and fibroblasts sense this crisis and release colony-stimulating factors or CSFs.
- CSFs have short half-lives of only a few hours; however, once bound to the progenitors, they determine their lineage-commitment choices, influencing them to differentiate into granulocytes or macrophages. CSFs also help the progenitors perform specific functions. There are four types of CSFs involved in CMP differentiation. They include: Granulocyte-macrophage colony-stimulating factor or GM-CSF,
- Granulocyte colony-stimulating factor or G-CSF,
- Macrophage colony-stimulating factor or M-CSF, and
- Interleukin-3 or IL-3, a multipotential colony-stimulating factor.
The GM-CSF and IL-3 trigger eosinophil production and help fight parasitic or allergic reactions. The G-CSF helps progenitors differentiate into granulocytes, while the M-CSF initiates macrophage production. Neutrophils and macrophages are phagocytic cells that attack the microbes and digest them through phagocytosis.
Recombinant G-CSF and GM-CSF injections are often administered as adjunct therapy to the cancer patient. They are subcutaneously injected to help replenish the lost immune cells and overcome side effects such as neutropenia (low level of neutrophils in the blood) and low white blood cell count, which are standard post chemotherapy or radiation therapy.
Leitura Sugerida
- Metcalf, D. (2010). The colony-stimulating factors and cancer. Nature Reviews Cancer, 10(6), 425-434.
- Barreda, D. R., Hanington, P. C., & Belosevic, M. (2004). Regulation of myeloid development and function by colony-stimulating factors. Developmental & Comparative Immunology, 28(5), 509-554.
- Alberts, B. (2017). Molecular biology of the cell. WW Norton & Company.
- Lodish, H., Berk, A., Kaiser, C. A., Kaiser, C., Krieger, M., Scott, M. P., … & Matsudaira, P. (2008). Molecular cell biology. Macmillan.