In the in vitro studies of hematopoietic cells, it was found that some cytokines can stimulate different hematopoietic stem cells to form cell colonies in semi-solid medium. Such factors are named colony-stimulating factors (CSF). According to the scope of colony-stimulating factors, they are named as 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 play a role in promoting proliferation and differentiation of hematopoietic stem cells at different developmental stages, and are essential stimulating factors for blood cell development. In a broad sense, all cytokines that stimulate hematopoietic can be collectively referred to as CSF, such as erythropoictin (Epo), stem cell factor (SCF) that stimulates hematopoietic stem cells, leukemia inhibitory that can stimulate embryonic stem cells factor, LIF), and thrombopoietin, which stimulate platelets, have colony-stimulating activity. In addition, CSF also acts on a variety of mature cells and promotes its heterogeneous function.
CSF-1, also called M-CSF, is a hematopoietic growth factor involved in the proliferation, differentiation, and survival of monocytes, macrophages, and bone marrow progenitor cells. M-CSF affects macrophages and monocytes in a variety of ways, including stimulation of increased phagocytosis and increased chemotactic activity, and increased cytotoxicity of tumor cells. The role of M-CSF is not limited to monocytes/macrophages. By interacting with its membrane receptors (CSF1R or M-CSF-R encoded by the c-fms proto-oncogene), M-CSF can also regulate the proliferation of early hematopoietic progenitor cells and affect immunology, metabolism, fertility and pregnancy Numerous physiological processes. M-CSF (parathyroid hormone stimulates endocrine) released by osteoblasts produces a paracrine effect on osteoclasts. M-CSF binds to receptors on osteoclasts, induces differentiation, and eventually absorbs (decomposes) bones leading to elevated plasma calcium levels . In addition, high levels of CSF-1 expression were observed in the endometrial epithelium of pregnant women's uterus, and high levels of CSF-1R receptors were observed in placental trophoblasts. Studies have shown that local high levels of CSF-1 activation of trophoblast CSF1R is essential for normal embryo implantation and placental development. Recently, CSF-1 and its receptor CSF1R have been found to be involved in the breast during normal development and tumor growth. Locally produced M-CSF on the vessel wall contributes to the development and progression of atherosclerosis.
GM-CSF is a monomeric glycoprotein that functions as a cytokine-it is a leukocyte growth factor. GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the cycle and migrate into tissues, where they mature into macrophages and dendritic cells. Therefore, it is part of the immune/inflammatory cascade, and through this activation, the activation of a small number of macrophages can quickly lead to an increase in their number, which is a key process in fighting infection. GM-CSF also has an effect on mature cells of macrophages. immune system. These include, for example, enhanced receptors that enhance neutrophil migration and cause cell surface expression. GM-CSF signals through signal transduction and transcriptional activator STAT5. It has also been shown to signal through STAT3 in macrophages. Cytokines activate macrophages to inhibit fungal survival. It induces the deprivation of free zinc in cells and increases the production of reactive oxygen species, which ultimately leads to zinc deficiency and toxicity in fungi. Therefore, GM-CSF promotes the development of the immune system and enhances its ability to fight infections. GM-CSF also plays the role of embryonic factors produced by the reproductive tract, and also plays a role in embryo development.
Figure 1. Structure of GM-CSF.
Granulocyte colony-stimulating factor (G-CSF or GCSF), also known as colony-stimulating factor 3 (CSF 3), is a glycoprotein that stimulates bone marrow to produce granulocytes and stem cells and releases them into the blood. Functionally, it is a cytokine and hormone, a colony-stimulating factor, produced by many different tissues. The naturally-occurring drug analogues of G-CSF are called felgrastim and lenaglastine. G-CSF also stimulates the survival, proliferation, differentiation and function of neutrophil precursors and mature neutrophils.
Figure 2. Structure of G-CSF.
In contrast to other membrane-bound substances in the hematopoietic microenvironment, colony-stimulating factors are soluble (permeable). It is sometimes used as a definition of CSF. They are transduced by paracrine, endocrine or autocrine signals.