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Colony-Stimulating Factor (CSF) & Receptor Proteins

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Colony-Stimulating Factor (CSF) & Receptor Proteins

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Colony-Stimulating Factor (CSF) & Receptor Proteins Background

Colony stimulating factor (CSF) is a kind of cytokine discovered by researchers in the study of hematopoietic cells in vitro. It can stimulate the proliferation and differentiation of pluripotent hematopoietic stem cells and hematopoietic progenitor cells at different stages of development and differentiation, and form corresponding cell colonies in semi-solid medium.

Schematic diagram of mononuclear macrophages and colony stimulating factors Fig.1 Schematic diagram of mononuclear macrophages and colony stimulating factors

Classification of colony stimulating factors

According to the range of colony stimulating factors, they were named granulocyte CSF (G-CSF), macrophage CSF (M-CSF), granulocyte and macrophage CSF (GM-CSF) and multipotent colony stimulating factor (multi-CSF, also known as IL-3). They are essential stimulants for the development of blood cells. Broadly speaking, all stimulate hematopoietic cytokines can be referred to as CSF, For example, erythropoietin (Epo), which stimulates the production of red blood cells, The stem cell factor (SCF) that stimulates the production of hematopoietic stem cells, Leukaemia suppressor (LIF), which stimulates the generation of embryonic stem cells, and thrombogenin, which stimulates thrombogenesis. These cytokines have colony stimulating activity, in addition, CSF also ACTS on a variety of mature cells, promoting their function to have a heterogeneous effect. With the deepening of the study, it was found that colony-stimulating factor could mobilize the migration of neutrophils from bone marrow to peripheral blood and promote the differentiation and proliferation of neutrophils precursors in bone marrow, enhance the function of neutrophils.

A family tree of colony-stimulating factors Fig.2 A family tree of colony-stimulating factors
  1. Interleukin IL-3 can stimulate the proliferation of skin epithelial cells, CD4- cd8-tcr stimulating cells, mast cells and basophils, and prevent the occurrence of programmed mast cell death.
  2. Stem cell factor (SCF), also known as mast cytokine, is a ligand of c-kit and mainly exists in transmembrane and secretory forms. SCF is mainly produced by bone marrow stromal cells, which can promote the proliferation and differentiation of il-3-dependent early hematopoietic progenitor cells, promote the proliferation of mast cells, and promote the proliferation of melanocytes.
  3. Flt3-ligand exists in transmembrane and secretory forms, which mainly come from stromal cells. Flt3-ligand stimulates the proliferation and differentiation of primitive hematopoietic stem cells.
  4. Erythropoietin (EPO) is a glycoprotein that stimulates red blood cells. Its main source is interstitial cells around the renal tubules. EPO promotes the differentiation of bone marrow red blood cell precursors into mature red blood cells. It can specifically act on red blood cell-like precursors and has little effect on other cell lines.
  5. Thrombopoietin (TPO), mainly from smooth muscle cells and endothelial cells. TPO stimulates bone marrow megakaryocytes to differentiate and mature into platelets.
  6. Macrophage colony stimulating factor (M-CSF), also known as csf-1, was initially found in serum, urine or other body fluids and is mainly produced by mononuclear macrophages, lymphocytes, endothelial cells, fibroblasts and epithelial cells. M-csf stimulates the proliferation and differentiation of mononuclear macrophages, prolongs their survival time and enhances their function. M-csf stimulates the formation of hematopoietic cells and macrophage colonies in bone marrow. M-csf can also promote the survival, proliferation and activation of osteoclasts. M-csf is a mediator in inflammatory response, which can improve the ability of macrophages to kill tumor cells and microorganisms.
  7. Granulocyte - macrophage colony stimulating factor (GM-CSF), also known as CSF2. The main cell sources are activated T cells, mononuclear macrophages, endothelial cells, fibroblasts and so on. GM-CSF mainly stimulates the growth and differentiation of bone marrow progenitor cells, stimulates the differentiation of bone marrow progenitor cells into granulocytes and monocytes, and promotes hematopoietic and eosinophil proliferation.
    GM-CSF protein structure diagram Fig.3 GM-CSF protein structure diagram

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a key role in the development and maturation of dendritic cells (DCS) and the proliferation and activation of T cells, which link innate and acquired immune responses. GM-CSF was expressed in mice treated with melanoma cells. An increase in the number of eosinophil, monocytes, macrophages, and lymphocytes can be observed in the lymph nodes. They led to a sustained anti-tumor response in the mice. GM-CSF was beneficial to the expansion of DC1 population and increased the DC - mediated response to tumor cells. In vitro studies of human myelogenous leukemia cells, GM-CSF not only promotes antigen presentation, but also directs cells to DC phenotypes. GM-CSF is also used to improve neutropenia after induction chemotherapy in elderly patients with acute myelogenous leukemia.

    Related functions of GM-CSF Fig.4 Related functions of GM-CSF
  8. Granulocyte colony-stimulating factor (G-CSF), also known as CSF-3, is a glycoprotein produced mainly by activated T cells, mononuclear macrophages, endothelial cells, and fibroblasts. G-CSF stimulates the differentiation and maturation of granulocyte progenitor cells, enhances the phagocytic killing function of mature granulocytes and prolongs their survival time. G-CSF stimulates the neutrophils precursors of bone marrow hematopoietic cells in vitro to differentiate and proliferate into mature granulocyte colonies. It also acts on fully mature terminal granulocytes, prolonging the survival time of mature neutrophils, improving the phagocytosis ability of neutrophils, and promoting the production of superoxide and the synthesis of alkaline phosphatase. As a hematopoietic growth factor, G-CSF can move cells from the bone marrow to the peripheral blood, and help improve the angiogenesis and regeneration of human myocardial perfusion and damaged myocardium. G-CSF is mainly used to prevent and treat leukopenia caused by radiotherapy or chemotherapy of tumor, treat hematopoietic dysfunction of bone marrow and myelodysplastic syndrome, prevent the possible complications of infection caused by leukopenia, and accelerate the recovery of neutropenia caused by infection.
Leukemia was treated with hematopoietic stem cell transplantation after G-CSF injection Fig.5 Leukemia was treated with hematopoietic stem cell transplantation after G-CSF injection

Conclusion

Studies have shown that colony-stimulating factors can stimulate the formation of neutral protease plasminogen activators in macrophages, and GM-CSF and M-CSF can be regarded as pro-inflammatory cytokines. CSF may form an important part of the "CSF network" in inflammatory states, associated with cerebrospinal fluid and the expression and role of the pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1). GM-CSF and M-CSF are expressed at higher levels in inflammatory and autoimmune sites, such as synovial fluid in patients with rheumatoid arthritis. There is further evidence linking the IL-23-IL-17 pathway to GM-CSF and G-CSF. Because of the association between inflammatory responses mediated by these other cytokines and certain diseases, such as rheumatoid arthritis, obesity, and cancer, CSF may also be associated with the pathogenesis of several diseases and conditions.

References:

  1. Lieschke G J, Burgess A W. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor[J]. New England Journal of Medicine, 1992, 327(1): 28-35.
  2. Sherr C J, Stanley E R. Colony-stimulating factor 1 (macrophage colony-stimulating-factor)[M]//Peptide Growth Factors and Their Receptors I. Springer, Berlin, Heidelberg, 1990: 667-698.
  3. Demetri G D, Griffin J D. Granulocyte colony-stimulating factor and its receptor[J]. Blood, 1991, 78(11): 2791-2808.
  4. Judith C. Molecular physiology of granulocyte-macrophage colony-stimulating factor[J]. Blood, 1991, 77: 1131-1145.

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