Macrophage colony-stimulating factor

Last updated
CSF1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CSF1 , CSF-1, MCSF, colony stimulating factor 1
External IDs OMIM: 120420 MGI: 1339753 HomoloGene: 7282 GeneCards: CSF1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_172212
NM_000757
NM_172210
NM_172211

NM_001113529
NM_001113530
NM_007778

RefSeq (protein)

NP_000748
NP_757349
NP_757350
NP_757351

NP_001107001
NP_001107002
NP_031804

Location (UCSC) Chr 1: 109.91 – 109.93 Mb Chr 3: 107.65 – 107.67 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The colony stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor (M-CSF), is a secreted cytokine which causes hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. It is one of the three experimentally described colony-stimulating factors. M-CSF binds to the colony stimulating factor 1 receptor. It may also be involved in development of the placenta. [5]

Contents

Structure

M-CSF is a cytokine, being a smaller protein involved in cell signaling. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors. [5]

Four transcript variants encoding three different isoforms (a proteoglycan, glycoprotein and cell surface protein) [6] have been found for this gene. [5]

Function

M-CSF (or CSF-1) is a hematopoietic growth factor that is involved in the proliferation, differentiation, and survival of monocytes, macrophages, and bone marrow progenitor cells. [7] M-CSF affects macrophages and monocytes in several ways, including stimulating increased phagocytic and chemotactic activity, and increased tumour cell cytotoxicity. [8] The role of M-CSF is not only restricted to the monocyte/macrophage cell lineage. By interacting with its membrane receptor (CSF1R or M-CSF-R encoded by the c-fms proto-oncogene), M-CSF also modulates the proliferation of earlier hematopoietic progenitors and influence numerous physiological processes involved in immunology, metabolism, fertility and pregnancy. [9]

M-CSF released by osteoblasts (as a result of endocrine stimulation by parathyroid hormone) exerts paracrine effects on osteoclasts. [10] M-CSF binds to receptors on osteoclasts inducing differentiation, and ultimately leading to increased plasma calcium levels—through the resorption (breakdown) of bone[ citation needed ]. Additionally, high levels of CSF-1 expression are observed in the endometrial epithelium of the pregnant uterus as well as high levels of its receptor CSF1R in the placental trophoblast. Studies have shown that activation of trophoblastic CSF1R by local high levels of CSF-1 is essential for normal embryonic implantation and placental development. More recently, it was discovered that CSF-1 and its receptor CSF1R are implicated in the mammary gland during normal development and neoplastic growth. [11]

Clinical significance

Locally produced M-CSF in the vessel wall contributes to the development and progression of atherosclerosis. [12]

M-CSF has been described to play a role in renal pathology including acute kidney injury and chronic kidney failure. [13] [14] The chronic activation of monocytes can lead to multiple metabolic, hematologic and immunologic abnormalities in patients with chronic kidney failure. [13] In the context of acute kidney injury, M-CSF has been implicated in promoting repair following injury, [15] but also been described in an opposing role, driving proliferation of a pro-inflammatory macrophage phenotype. [16]

As a drug target

PD-0360324 and MCS110 are CSF1 inhibitors in clinical trials for some cancers. [17] See also CSF1R inhibitors.

Interactions

Macrophage colony-stimulating factor has been shown to interact with PIK3R2. [18]

Related Research Articles

<span class="mw-page-title-main">Cytokine</span> Broad and loose category of small proteins important in cell signaling

Cytokines are a broad and loose category of small proteins important in cell signaling. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptors on the target cell surface. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents.

<span class="mw-page-title-main">Macrophage</span> Type of white blood cell

Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.

<span class="mw-page-title-main">Monocyte</span> Subtype of leukocytes

Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also influence adaptive immune responses and exert tissue repair functions. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.

<span class="mw-page-title-main">Granulocyte colony-stimulating factor</span> Mammalian protein found in humans

Granulocyte colony-stimulating factor, also known as colony-stimulating factor 3, is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.

Interleukins (ILs) are a group of cytokines that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related proteins.

<span class="mw-page-title-main">Granulocyte-macrophage colony-stimulating factor</span> Mammalian protein found in Homo sapiens

Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts that functions as a cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim.

<span class="mw-page-title-main">Interleukin 3</span> Protein-coding gene in the species Homo sapiens

Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene localized on chromosome 5q31.1. Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: the protein contains 152 amino acids and its molecular weight is 17 kDa. IL-3 is produced as a monomer by activated T cells, monocytes/macrophages and stroma cells. The major function of IL-3 cytokine is to regulate the concentrations of various blood-cell types. It induces proliferation and differentiation in both early pluripotent stem cells and committed progenitors. It also has many more specific effects like the regeneration of platelets and potentially aids in early antibody isotype switching.

Interleukin 5 (IL-5) is an interleukin produced by type-2 T helper cells and mast cells.

<span class="mw-page-title-main">CCL2</span> Mammalian protein found in Homo sapiens

The chemokine ligand 2 (CCL2) is also referred to as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2. CCL2 is a small cytokine that belongs to the CC chemokine family. CCL2 tightly regulates cellular mechanics and thereby recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation produced by either tissue injury or infection.

<span class="mw-page-title-main">Granulopoiesis</span> Part of haematopoiesis, that leads to the production of granulocytes

Granulopoiesis is a part of haematopoiesis, that leads to the production of granulocytes. A granulocyte, also referred to as a polymorphonuclear leukocyte (PMN), is a type of white blood cell that has multi lobed nuclei, usually containing three lobes, and has a significant amount of cytoplasmic granules within the cell. Granulopoiesis takes place in the bone marrow. It leads to the production of three types of mature granulocytes: neutrophils, eosinophils and basophils.

<span class="mw-page-title-main">Interleukin 15</span> Cytokine with structural similarity to Interleukin-2

Interleukin-15 (IL-15) is a protein that in humans is encoded by the IL15 gene. IL-15 is an inflammatory cytokine with structural similarity to Interleukin-2 (IL-2). Like IL-2, IL-15 binds to and signals through a complex composed of IL-2/IL-15 receptor beta chain (CD122) and the common gamma chain. IL-15 is secreted by mononuclear phagocytes following infection by virus(es). This cytokine induces the proliferation of natural killer cells, i.e. cells of the innate immune system whose principal role is to kill virally infected cells.

Chemokine ligands 4 previously known as macrophage inflammatory protein (MIP-1β), is a protein which in humans is encoded by the CCL4 gene. CCL4 belongs to a cluster of genes located on 17q11-q21 of the chromosomal region. Identification and localization of the gene on the chromosome 17 was in 1990 although the discovery of MIP-1 was initiated in 1988 with the purification of a protein doublet corresponding to inflammatory activity from supernatant of endotoxin-stimulated murine macrophages. At that time, it was also named as "macrophage inflammatory protein-1" (MIP-1) due to its inflammatory properties.

<span class="mw-page-title-main">Granulocyte colony-stimulating factor receptor</span> Protein-coding gene in the species Homo sapiens

The granulocyte colony-stimulating factor receptor (G-CSF-R) also known as CD114 is a protein that in humans is encoded by the CSF3R gene. G-CSF-R is a cell-surface receptor for the granulocyte colony-stimulating factor (G-CSF). The G-CSF receptors belong to a family of cytokine receptors known as the hematopoietin receptor family. The granulocyte colony-stimulating factor receptor is present on precursor cells in the bone marrow, and, in response to stimulation by G-CSF, initiates cell proliferation and differentiation into mature neutrophilic granulocytes and macrophages.

THP-1 is a human monocytic cell line derived from an acute monocytic leukemia patient. It is used to test leukemia cell lines in immunocytochemical analysis of protein-protein interactions, and immunohistochemistry.

<span class="mw-page-title-main">Granulocyte-macrophage colony-stimulating factor receptor</span> Protein-coding gene in humans

The granulocyte-macrophage colony-stimulating factor receptor, also known as CD116, is a receptor for granulocyte-macrophage colony-stimulating factor, which stimulates the production of white blood cells. In contrast to M-CSF and G-CSF which are lineage specific, GM-CSF and its receptor play a role in earlier stages of development. The receptor is primarily located on neutrophils, eosinophils and monocytes/macrophages, it is also on CD34+ progenitor cells (myeloblasts) and precursors for erythroid and megakaryocytic lineages, but only in the beginning of their development.

<span class="mw-page-title-main">Colony stimulating factor 1 receptor</span> Protein found in humans

Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115, is a cell-surface protein encoded by the human CSF1R gene. CSF1R is a receptor that can be activated by two ligands: colony stimulating factor 1 (CSF-1) and interleukin-34 (IL-34). CSF1R is highly expressed in myeloid cells, and CSF1R signaling is necessary for the survival, proliferation, and differentiation of many myeloid cell types in vivo and in vitro. CSF1R signaling is involved in many diseases and is targeted in therapies for cancer, neurodegeneration, and inflammatory bone diseases.

<span class="mw-page-title-main">IL3RA</span> Human gene

Interleukin 3 receptor, alpha (IL3RA), also known as CD123, is a human gene.

The interleukin-5 receptor is a type I cytokine receptor. It is a heterodimer of the interleukin 5 receptor alpha subunit and CSF2RB.

An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule that is secreted from immune cells like helper T cells (Th) and macrophages, and certain other cell types that promote inflammation. They include interleukin-1 (IL-1), IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNF-α), interferon gamma (IFNγ), and granulocyte-macrophage colony stimulating factor (GM-CSF) and play an important role in mediating the innate immune response. Inflammatory cytokines are predominantly produced by and involved in the upregulation of inflammatory reactions.

<span class="mw-page-title-main">Emactuzumab</span> Monoclonal antibody

Emactuzumab (RG-7155) is a humanized monoclonal antibody directed against colony stimulating factor 1 receptor (CSF-1R) expressed on macrophages and has demonstrated a profound antitumor effect through interference with the CSF-1/CSF-1R axis, along with a manageable safety profile in patients with diffuse-type tenosynovial giant cell tumors (d-TGCT).

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000184371 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000014599 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 "Entrez Gene: CSF1 colony stimulating factor 1 (macrophage)".
  6. Jang MH, Herber DM, Jiang X, Nandi S, Dai XM, Zeller G, Stanley ER, Kelley VR (September 2006). "Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation". Journal of Immunology. 177 (6): 4055–63. doi: 10.4049/jimmunol.177.6.4055 . PMID   16951369.
  7. Stanley ER, Berg KL, Einstein DB, Lee PS, Pixley FJ, Wang Y, Yeung YG (January 1997). "Biology and action of colony--stimulating factor-1". Molecular Reproduction and Development. 46 (1): 4–10. doi:10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V. PMID   8981357. S2CID   20846803.
  8. Nemunaitis J (April 1993). "Macrophage function activating cytokines: potential clinical application". Critical Reviews in Oncology/Hematology. 14 (2): 153–71. doi:10.1016/1040-8428(93)90022-V. PMID   8357512.
  9. Fixe P, Praloran V (June 1997). "Macrophage colony-stimulating-factor (M-CSF or CSF-1) and its receptor: structure-function relationships". European Cytokine Network. 8 (2): 125–36. PMID   9262961.
  10. Han Y, You X, Xing W, Zhang Z, Zou W (2018). "Paracrine and endocrine actions of bone—the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts". Bone Research. 6: 16. doi:10.1038/s41413-018-0019-6. PMC   5967329 . PMID   29844945.
  11. Sapi E (January 2004). "The role of CSF-1 in normal physiology of mammary gland and breast cancer: an update". Experimental Biology and Medicine. 229 (1): 1–11. doi:10.1177/153537020422900101. PMID   14709771. S2CID   30541196.
  12. Rajavashisth T, Qiao JH, Tripathi S, Tripathi J, Mishra N, Hua M, Wang XP, Loussararian A, Clinton S, Libby P, Lusis A (June 1998). "Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice". The Journal of Clinical Investigation. 101 (12): 2702–10. doi:10.1172/JCI119891. PMC   508861 . PMID   9637704.
  13. 1 2 Le Meur Y, Fixe P, Aldigier JC, Leroux-Robert C, Praloran V (September 1996). "Macrophage colony stimulating factor involvement in uremic patients". Kidney International. 50 (3): 1007–12. doi: 10.1038/ki.1996.402 . PMID   8872977.
  14. Lim GB (2013-01-01). "Acute kidney injury: CSF-1 signalling is involved in repair following AKI". Nature Reviews Nephrology. 9 (1): 2. doi: 10.1038/nrneph.2012.253 . ISSN   1759-5061. PMID   23165301. S2CID   38517528.
  15. Zhang MZ, Yao B, Yang S, Jiang L, Wang S, Fan X, Yin H, Wong K, Miyazawa T, Chen J, Chang I, Singh A, Harris RC (December 2012). "CSF-1 signaling mediates recovery from acute kidney injury". The Journal of Clinical Investigation. 122 (12): 4519–32. doi:10.1172/JCI60363. PMC   3533529 . PMID   23143303.
  16. Cao Q, Wang Y, Zheng D, Sun Y, Wang C, Wang XM, Lee VW, Wang Y, Zheng G, Tan TK, Wang YM, Alexander SI, Harris DC (April 2014). "Failed renoprotection by alternatively activated bone marrow macrophages is due to a proliferation-dependent phenotype switch in vivo". Kidney International. 85 (4): 794–806. doi: 10.1038/ki.2013.341 . PMID   24048378.
  17. Interest Builds in CSF1R for Targeting Tumor Microenvironment
  18. Gout I, Dhand R, Panayotou G, Fry MJ, Hiles I, Otsu M, Waterfield MD (December 1992). "Expression and characterization of the p85 subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system". The Biochemical Journal. 288 (2): 395–405. doi:10.1042/bj2880395. PMC   1132024 . PMID   1334406.

Further reading