Factor estimulante de colonias de macrófagos

PDB 1hmc
Factor estimulante de colonias 1 (macrófago)
Identificadores
Símbolo	MCSF
Símbolos alt.	CSF1 ; CSF-1; M-CSF
Entrez	1435
OMIM	120420
RefSeq	NP_000748
UniProt	P09603
Outros datos
Locus	Cr. 1 :(110.45 – 110.47 Mb)

O factor estimulante de colonias de macrófagos (M-CSF, do inglés Macrophague colony-stimulating factor), tamén chamado factor estimulante de colonias 1 (CSF1), é unha citocina segregada reguladora, que inflúe nas células nai hematopoéticas para que se diferencien en macrófagos ou outros tipos celulares relacionados. As células eucarióticas tamén producen o M-CSF para combater as infeccións virais intracelulares. Pode estar tamén implicado no desenvolvemento da placenta.^[1] O M-CSF (ou CSF1) únese a un receptor da superficie celular chamado receptor do factor estimulante de colonias 1.

Estrutura

O M-CSF é unha citocina. A forma activa da proteína encóntrase extracelularmente como un homodímero unido por ponte disulfuro, e crese que se produce por clivaxe proteolítica de precursores unidos a membrana.^[1]

Atopáronse catro variantes de transcrición do xene desta proteína, que codifican tres isoformas.^[1]

Función

O M-CSF (ou CSF1) é un factor de crecemento hematopoético que está implicado na proliferación, diferenciación e supervivencia de monocitos, macrófagos, e células proxenitoras da medula ósea.^[2] O M-CSF afecta a macrófagos e a monocitos de varios modos, incluíndo o estímulo do incremento da actividade quimiotáctica e fagocítica, e o incremento da citotoxicidade en células tumorais.^[3] A función do M-CSF non está restrinxida á liñaxe celular de monocitos/macrófagos. Ao interaccionar co seu receptor de membrana (o CSF1R ou M-CSF-R codificado polo protooncoxene c-fms), o M-CSF tamén modula a proliferación de proxenitores hematopoéticos temperáns e inflúe en numerosos procesos fisiolóxicos implicados en inmunoloxía, metabolismo, fertilidade e embarazo.^[4]

O M-CSF liberado polos osteoblastos (como resultado da estimulación endócrina pola hormona paratiroide) exerce efectos parácrinos sobre os osteoclastos. O M-CSF únese a receptores situados na superficie dos osteoclastos inducindo a diferenciación, e finalmente orixina o incremento no plasma dos niveis de calcio, por medio da resorción ósea. Adicionalmente, obsérvase un alto nivel de expresión de M-CSF (ou CSF1) no epitelio endometrial do útero grávido, e tamén un alto nivel do seu receptor CSF1R no trofoblasto placentario. A activación do CSF1R trofoblástico por niveis locais altos de M-CSF (ou CSF1) é esencial para a implantación normal do embrión e o desenvolvemento placentario. Máis recentemente, descubriuse que este factor proteico e o seu receptor están implicados no desenvolvemento normal e no crecemento neoplásico da glándula mamaria.^[5]

Importancia clínica

O M-CSF producido localmente na parede dos vasos sanguíneos contribúe ao desenvolvemento e progresión da aterosclerose.^[6]

Ademais, o M-CSF xoga un papel na activación crónica de monocitos, a cal orixina moitas anormalidades metabólicas, hematolóxicas e inmunolóxicas en pacientes con insuficiencia renal crónica.^[7]

Interacción

O M-CSF presenta interaccións con PIK3R2.^[8]

Notas

↑ ^1,0 ^1,1 ^1,2 "Entrez Gene: CSF1 colony stimulating factor 1 (macrophage)".
↑ Stanley ER, Berg KL, Einstein DB, Lee PS, Pixley FJ, Wang Y, Yeung YG (January 1997). "Biology and action of colony--stimulating factor-1". Mol. Reprod. Dev. 46 (1): 4–10. PMID 8981357. doi:10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V.
↑ Nemunaitis J (April 1993). "Macrophage function activating cytokines: potential clinical application". Crit. Rev. Oncol. Hematol. 14 (2): 153–71. PMID 8357512. doi:10.1016/1040-8428(93)90022-V.
↑ Fixe P, Praloran V (June 1997). "Macrophage colony-stimulating-factor (M-CSF or CSF-1) and its receptor: structure-function relationships". Eur. Cytokine Netw. 8 (2): 125–36. PMID 9262961.
↑ Sapi E (January 2004). "The role of CSF-1 in normal physiology of mammary gland and breast cancer: an update". Exp. Biol. Med. (Maywood) 229 (1): 1–11. PMID 14709771.
↑ 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". J. Clin. Invest. 101 (12): 2702–10. PMC 508861. PMID 9637704. doi:10.1172/JCI119891.
↑ Le Meur Y., Fixe P., Aldigier J-C., Leroux-Robert C. and Praloran V. (April 1996). "Macrophage colony stimulating factor involvement in uremic patients". Kidney International 50 (196): 1107–1102. doi:10.1038/ki.1996.402.
↑ 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". Biochem. J. 288 (2): 395–405. PMC 1132024. PMID 1334406.

Véxase tamén

Bibliografía

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". J. Clin. Invest. 101 (12): 2702–10. PMC 508861. PMID 9637704. doi:10.1172/JCI119891.
Stanley ER, Berg KL, Einstein DB, Lee PS, Yeung YG (1995). "The biology and action of colony stimulating factor-1". Stem Cells. 12 Suppl 1: 15–24; discussion 25. PMID 7696959.
Alterman RL, Stanley ER (1994). "Colony stimulating factor-1 expression in human glioma". Mol. Chem. Neuropathol. 21 (2–3): 177–88. PMID 8086034. doi:10.1007/BF02815350.
Stanley ER, Berg KL, Einstein DB, Lee PS, Pixley FJ, Wang Y, Yeung YG (1997). "Biology and action of colony--stimulating factor-1". Mol. Reprod. Dev. 46 (1): 4–10. PMID 8981357. doi:10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V.
Sweet MJ, Hume DA (2004). "CSF-1 as a regulator of macrophage activation and immune responses". Arch. Immunol. Ther. Exp. (Warsz.) 51 (3): 169–77. PMID 12894871.
Mroczko B, Szmitkowski M (2005). "Hematopoietic cytokines as tumor markers". Clin. Chem. Lab. Med. 42 (12): 1347–54. PMID 15576295. doi:10.1515/CCLM.2004.253.
Pandit J, Bohm A, Jancarik J, Halenbeck R, Koths K, Kim SH (1993). "Three-dimensional structure of dimeric human recombinant macrophage colony-stimulating factor". Science 258 (5086): 1358–62. PMID 1455231. doi:10.1126/science.1455231.
Suzu S, Ohtsuki T, Yanai N, Takatsu Z, Kawashima T, Takaku F, Nagata N, Motoyoshi K (1992). "Identification of a high molecular weight macrophage colony-stimulating factor as a glycosaminoglycan-containing species". J. Biol. Chem. 267 (7): 4345–8. PMID 1531650.
Saltman DL, Dolganov GM, Hinton LM, Lovett M (1992). "Reassignment of the human macrophage colony stimulating factor gene to chromosome 1p13-21". Biochem. Biophys. Res. Commun. 182 (3): 1139–43. PMID 1540160. doi:10.1016/0006-291X(92)91850-P.
Praloran V, Chevalier S, Gascan H (1992). "Macrophage colony-stimulating factor is produced by activated T lymphocytes in vitro and is detected in vivo in T cells from reactive lymph nodes". Blood 79 (9): 2500–1. PMID 1571567.
Price LK, Choi HU, Rosenberg L, Stanley ER (1992). "The predominant form of secreted colony stimulating factor-1 is a proteoglycan". J. Biol. Chem. 267 (4): 2190–9. PMID 1733926.
Pampfer S, Tabibzadeh S, Chuan FC, Pollard JW (1992). "Expression of colony-stimulating factor-1 (CSF-1) messenger RNA in human endometrial glands during the menstrual cycle: molecular cloning of a novel transcript that predicts a cell surface form of CSF-1". Mol. Endocrinol. 5 (12): 1931–8. PMID 1791839. doi:10.1210/mend-5-12-1931.
Stein J, Borzillo GV, Rettenmier CW (1990). "Direct stimulation of cells expressing receptors for macrophage colony-stimulating factor (CSF-1) by a plasma membrane-bound precursor of human CSF-1". Blood 76 (7): 1308–14. PMID 2145044.
Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER (1985). "The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1". Cell 41 (3): 665–76. PMID 2408759. doi:10.1016/S0092-8674(85)80047-7.
Cerretti DP, Wignall J, Anderson D, Tushinski RJ, Gallis BM, Stya M, Gillis S, Urdal DL, Cosman D (1988). "Human macrophage-colony stimulating factor: alternative RNA and protein processing from a single gene". Mol. Immunol. 25 (8): 761–70. PMID 2460758. doi:10.1016/0161-5890(88)90112-5.
Takahashi M, Hirato T, Takano M, Nishida T, Nagamura K, Kamogashira T, Nakai S, Hirai Y (1989). "Amino-terminal region of human macrophage colony-stimulating factor (M-CSF) is sufficient for its in vitro biological activity: molecular cloning and expression of carboxyl-terminal deletion mutants of human M-CSF". Biochem. Biophys. Res. Commun. 161 (2): 892–901. PMID 2660794. doi:10.1016/0006-291X(89)92683-1.
Kawasaki ES, Ladner MB, Wang AM, Van Arsdell J, Warren MK, Coyne MY, Schweickart VL, Lee MT, Wilson KJ, Boosman A (1985). "Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1)". Science 230 (4723): 291–6. PMID 2996129. doi:10.1126/science.2996129.
Rettenmier CW, Roussel MF, Ashmun RA, Ralph P, Price K, Sherr CJ (1987). "Synthesis of membrane-bound colony-stimulating factor 1 (CSF-1) and downmodulation of CSF-1 receptors in NIH 3T3 cells transformed by cotransfection of the human CSF-1 and c-fms (CSF-1 receptor) genes". Mol. Cell. Biol. 7 (7): 2378–87. PMC 365369. PMID 3039346.
Takahashi M, Hong YM, Yasuda S, Takano M, Kawai K, Nakai S, Hirai Y (1988). "Macrophage colony-stimulating factor is produced by human T lymphoblastoid cell line, CEM-ON: identification by amino-terminal amino acid sequence analysis". Biochem. Biophys. Res. Commun. 152 (3): 1401–9. PMID 3259875. doi:10.1016/S0006-291X(88)80441-8.
Rettenmier CW, Roussel MF (1989). "Differential processing of colony-stimulating factor 1 precursors encoded by two human cDNAs". Mol. Cell. Biol. 8 (11): 5026–34. PMC 365596. PMID 3264877.
Wong GG, Temple PA, Leary AC, Witek-Giannotti JS, Yang YC, Ciarletta AB, Chung M, Murtha P, Kriz R, Kaufman RJ (1987). "Human CSF-1: molecular cloning and expression of 4-kb cDNA encoding the human urinary protein". Science 235 (4795): 1504–8. PMID 3493529. doi:10.1126/science.3493529.

Outros artigos

Factor estimulante de colonias, outros CSF

Ligazóns externas

Macrophage Colony-Stimulating Factor Medical Subject Headings (MeSH) na Biblioteca Nacional de Medicina dos EUA.

[entrezgene-1] 1,0 ^1,1 ^1,2 "Entrez Gene: CSF1 colony stimulating factor 1 (macrophage)".

[pmid8981357-2] Stanley ER, Berg KL, Einstein DB, Lee PS, Pixley FJ, Wang Y, Yeung YG (January 1997). "Biology and action of colony--stimulating factor-1". Mol. Reprod. Dev. 46 (1): 4–10. PMID 8981357. doi:10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V.

[pmid8357512-3] Nemunaitis J (April 1993). "Macrophage function activating cytokines: potential clinical application". Crit. Rev. Oncol. Hematol. 14 (2): 153–71. PMID 8357512. doi:10.1016/1040-8428(93)90022-V.

[pmid9262961-4] Fixe P, Praloran V (June 1997). "Macrophage colony-stimulating-factor (M-CSF or CSF-1) and its receptor: structure-function relationships". Eur. Cytokine Netw. 8 (2): 125–36. PMID 9262961.

[pmid14709771-5] Sapi E (January 2004). "The role of CSF-1 in normal physiology of mammary gland and breast cancer: an update". Exp. Biol. Med. (Maywood) 229 (1): 1–11. PMID 14709771.

[pmid9637704-6] 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". J. Clin. Invest. 101 (12): 2702–10. PMC 508861. PMID 9637704. doi:10.1172/JCI119891.

[doi_=_10.1038/ki.1996.402-7] Le Meur Y., Fixe P., Aldigier J-C., Leroux-Robert C. and Praloran V. (April 1996). "Macrophage colony stimulating factor involvement in uremic patients". Kidney International 50 (196): 1107–1102. doi:10.1038/ki.1996.402.

[pmid1334406-8] 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". Biochem. J. 288 (2): 395–405. PMC 1132024. PMID 1334406.

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