顆粒球マクロファージコロニー刺激因子 granulocyte-macrophage colony-stimulating factor

WordNet

the 3rd letter of the Roman alphabet (同)c
(music) the keynote of the scale of C major
a general-purpose programing language closely associated with the UNIX operating system
the 7th letter of the Roman alphabet (同)g

PrepTutorEJDIC

carbonの化学記号

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/04/05 15:24:52」(JST)

wiki en

Granulocyte macrophage colony-stimulating factor
Systematic (IUPAC) name

Human granulocyte macrophage colony stimulating factor
Clinical data
Identifiers
CAS Registry Number	83869-56-1^Y
ATC code	L03AA09
DrugBank	DB00020^N
Chemical data
Formula	C₆₃₉H₁₀₀₆N₁₆₈O₁₉₆S₈
Molecular mass	14434.5 g/mol
N (what is this?) (verify)

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, NK cells, endothelial cells and fibroblasts that functions as a cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim.

Function

GM-CSF is a monomeric glycoprotein that functions as a cytokine - it is a white blood cell growth factor.^[1] GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and dendritic cells. Thus, it is part of the immune/inflammatory cascade, by which activation of a small number of macrophages can rapidly lead to an increase in their numbers, a process crucial for fighting infection. GM-CSF signals via signal transducer and activator of transcription, STAT5.^[2]

GM-CSF signals via signal transducer and activator of transcription, STAT5. In macrophages, it has also been shown to signal via STAT3. The cytokine activates macrophages to inhibit fungal survival. It induces deprivation in intracellular free zinc and increases production of reactive oxygen species that culminate in fungal zinc starvation and toxicity.^[3] Thus, GM-CSF facilitates development of the immune system and promotes defense against infections.

GM-CSF also plays a role in embryonic development by functioning as an embryokine produced by reproductive tract.^[4]

Genetics

The human gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Genes in the cluster include those encoding interleukins 4, 5, and 13.^[5]

Glycosylation

Human granulocyte macrophage colony-stimulating factor is glycosylated in its mature form.

Medical use

GM-CSF is manufactured using recombinant DNA technology and is marketed as a protein therapeutic called molgramostim or, when the protein is expressed in yeast cells, sargramostim. It is used as a medication to stimulate the production of white blood cells and thus prevent neutropenia following chemotherapy.^[6]

GM-CSF has also recently been evaluated in clinical trials for its potential as a vaccine adjuvant in HIV-infected patients. The preliminary results have been promising^[7] but GM-CSF is not presently FDA-approved for this purpose.

Sargramostim

Sargramostim, recombinant yeast-derived GM-CSF developed at Immunex (now Amgen) and first given to six humans in 1987 as part of a compassionate-use protocol for the victims of cesium irradiation from the Goiânia accident.^[8] It was originally developed by Immunex. When Amgen bought Immunex, sargramostim was divested to Berlex, a US subsidiary of Schering AG. Berlex was acquired by Bayer in 2006, and Bayer sold the franchise to Genzyme in 2009, which was subsequently acquired by Sanofi.^[9] Its use was approved by U.S. Food and Drug Administration for acceleration of white blood cell recovery following autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma, acute lymphocytic leukemia, or Hodgkin's disease in March 1991.^[10] In November 1996, the FDA also approved sargramostim for treatment of fungal infections and replenishment of white blood cells following chemotherapy.^[11]

Rheumatoid arthritis

GM-CSF is found in high levels in joints with rheumatoid arthritis and blocking GM-CSF may reduce the inflammation or damage. Some drugs (e.g. MOR103) are being developed to block GM-CSF.^[12]

References

^ Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, Mata-Espinosa D, Marquina-Castillo B, Barrios-Payan J et al. (Jan 2014). "Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor". Medical Oncology 31 (1): 774. doi:10.1007/s12032-013-0774-6. PMID 24264600.
^ Voehringer D (Oct 2012). "Basophil modulation by cytokine instruction". European Journal of Immunology 42 (10): 2544–50. doi:10.1002/eji.201142318. PMID 23042651.
^ Subramanian Vignesh K, Landero Figueroa JA, Porollo A, Caruso JA, Deepe GS (Oct 2013). "Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival". Immunity 39 (4): 697–710. doi:10.1016/j.immuni.2013.09.006. PMC 3841917. PMID 24138881.
^ Hansen PJ, Dobbs KB, Denicol AC (Sep 2014). "Programming of the preimplantation embryo by the embryokine colony stimulating factor 2". Animal Reproduction Science 149 (1-2): 59–66. doi:10.1016/j.anireprosci.2014.05.017. PMID 24954585.
^ "Entrez Gene: CSF2 colony stimulating factor 2 (granulocyte-macrophage)".
^ Vacchelli E, Eggermont A, Fridman WH, Galon J, Zitvogel L, Kroemer G et al. (Jul 2013). "Trial Watch: Immunostimulatory cytokines". Oncoimmunology 2 (7): e24850. doi:10.4161/onci.24850. PMC 3782010. PMID 24073369.
^ Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ et al. (Sep 2011). "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans". Nature 477 (7362): 99–102. doi:10.1038/nature10358. PMID 21886163.
^ Schmeck HM (1987-11-02). "Radiation Team Sent to Brazil Saves Two With a New Drug". New York Times. Retrieved 2012-06-20.
^ Stewart Lyman for Xcocomy. June 11, 2010 Biotech Drug Discovery in Seattle: A Look Back
^ "Approval Summary for sargramostim". Oncology Tools. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. 1991-03-05. Archived from the original on 2007-09-29. Retrieved 20 September 2009.
^ "Newly Approved Drug Therapies (179): Leukine (sargramostim), Immunex". CenterWatch. Retrieved 2008-10-12.
^ Deiß A, Brecht I, Haarmann A, Buttmann M (Mar 2013). "Treating multiple sclerosis with monoclonal antibodies: a 2013 update". Expert Review of Neurotherapeutics 13 (3): 313–35. doi:10.1586/ern.13.17. PMID 23448220. Vancouver style error (help)

External links

Official gentaur web site
Official Leukine web site
Granulocyte-Macrophage Colony-Stimulating Factor at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 骨髄造血の制御 regulation of myelopoiesis
2. 化学療法による好中球減少症を有する成人患者と、急性白血病、骨髄異形成症候群、造血細胞移植以外の病態を有する成人患者における顆粒球コロニー刺激因子の利用 use of granulocyte colony stimulating factors in adult patients with chemotherapy induced neutropenia and conditions other than acute leukemia myelodysplastic syndrome and hematopoietic cell transplantation
3. 組換え造血成長因子の概要 introduction to recombinant hematopoietic growth factors
4. 造血細胞移植後の造血の促進 hematopoietic support after hematopoietic cell transplantation
5. 成人における肺胞蛋白症の診断および治療 diagnosis and treatment of pulmonary alveolar proteinosis in adults

English Journal

Peyer's patch-mediated intestinal immune system modulating activity of pectic-type polysaccharide from peel of Citrus unshiu.

Suh HJ, Yang HS, Ra KS, Noh DO, Kwon KH, Hwang JH, Yu KW.SourceDepartment of Food and Nutrition, Korea University, Seoul 136-703, Republic of Korea.
Food chemistry.Food Chem.2013 Jun 1;138(2-3):1079-86. doi: 10.1016/j.foodchem.2012.11.091. Epub 2012 Nov 29.
An intestinal immune system modulating polysaccharide (CUI-3IIb-3-2, 18kDa) was purified from Citrus unshiu peel. CUI-3IIb-3-2 mainly comprised GalA, GlcA, Ara, Gal and Rha, and it consisted of 4-linked GalA, terminal Araf, 4- or 5-linked/3,4- or 3,5-branched Ara, terminal Gal, and 2-linked/2,4-bran
PMID 23411217

Granulocyte macrophage colony-stimulating factor promotes regeneration of retinal ganglion cells in vitro through a mammalian target of rapamycin-dependent mechanism.

Legacy J, Hanea S, Theoret J, Smith PD.SourceDepartment of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Journal of neuroscience research.J Neurosci Res.2013 Jun;91(6):771-9. doi: 10.1002/jnr.23205. Epub 2013 Mar 4.
Lack of regeneration in the adult central nervous system (CNS) is a major hurdle that limits recovery from neurological ailments. Although accumulating research suggests the possibility of axon regeneration by targeting intrinsic signaling mechanisms, it remains a matter of controversy whether funct
PMID 23456828

Japanese Journal

抗GM-CSF受容体抗体 (特集リウマチ治療薬の新展開)

仁科直,竹内勤
医薬ジャーナル 48(6), 85-88, 2012-06
NAID 40019349556

3)免疫機構から見た流産の病態解明とその対策(シンポジウム1「流産の原因と対策」,第63回日本産科婦人科学会・学術講演会)

福井淳史
日本産科婦人科學會雜誌 63(12), 2167-2184, 2011-12-01
… However, proportion of CD56^<bright>/IFN-γ^+/TNF-α^+ cells and the TNF-α/GM-CSF expressing CD56^<bright> …
NAID 110008799036

Related Pictures

★リンクテーブル★

リンク元	「サイトカイン」「ホジキンリンパ腫」「サイトカイン受容体」「マクロファージ」「granulocyte-macrophage colony-stimulating factor」
拡張検索	「GM-CSF receptor」「GM-CSF受容体」「GM-CSFレセプター」
関連記事	「CS」「C」「CSF」「G」

「サイトカイン」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Granulocyte-macrophage colony-stimulating factor
	three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor
Identifiers
Symbol	GM_CSF
Pfam	PF01109
Pfam clan	CL0053
InterPro	IPR000773
PROSITE	PDOC00584
SCOP	2gmf
SUPERFAMILY	2gmf
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Colony stimulating factor 2 (granulocyte-macrophage)
	; PDB rendering based on 2gmf
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1CSG, 2GMF, 3CXE
Identifiers
Symbols	CSF2 ; GMCSF
External IDs	OMIM: 138960 MGI: 1339752 HomoloGene: 600 GeneCards: CSF2 Gene
Gene ontology
Molecular function	• cytokine activity; • granulocyte macrophage colony-stimulating factor receptor binding; • protein binding; • growth factor activity;
Cellular component	• extracellular region; • extracellular space;
Biological process	• embryonic placenta development; • immune response; • positive regulation of cell proliferation; • positive regulation of gene expression; • positive regulation of macrophage derived foam cell differentiation; • positive regulation of interleukin-23 production; • epithelial fluid transport; • macrophage activation; • positive regulation of tyrosine phosphorylation of Stat5 protein; • myeloid dendritic cell differentiation; • positive regulation of DNA replication; • negative regulation of cytolysis; • cellular response to lipopolysaccharide; • positive regulation of podosome assembly; • dendritic cell differentiation; • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

cyto=cell kin(e)=small substance

ex. manikine

細胞が分泌する糖タンパク質で、生物活性(増殖・分化・タンパク産生誘導などを)を有するもの

英: cytokine, cytokines
関: サイトカイン受容体、インターロイキン、リンホカイン

生態情報伝達方式

傍分泌系、自己分泌系により情報を伝達する。局所ホルモンともいえる(ホルモンは血流を介して他臓器に働く)

産生細胞・機能による分類名

機能

機能	サブグループ	サイトカイン	標的	機能
炎症性サイトカイン	TNFファミリー	TNF-α	白血球、上皮細胞	活性化
	インターロイキン	IL-1	上皮細胞、リンパ球	活性化
		IL-6	種々の細胞	活性化
		IL-8	白血球	炎症部位遊走
T細胞の増殖・分化	インターロイキン	IL-2	T細胞	活性化。増殖
		IL-4	T細胞	増殖
		IL-4	Th2細胞	分化誘導
		IL-12	Th1細胞	分化誘導
	インターフェロン	IFN-γ	Th2細胞	分化抑制
B細胞の増殖・分化	インターロイキン	IL-2	B細胞	活性化
		IL-4	B細胞	活性化、増殖、分化
		IL-5	B細胞	活性化、増殖
		IL-6	B細胞	増殖、分化
		TGF-β	B細胞	分化(IgA分泌)
アレルギー調節サイトカイン	インターロイキン	IL-3	肥満細胞	増殖、分化促進
		IL-4	B細胞	IgEクラススイッチ促進
		IL-5	好酸球	増殖、分化促進
		IL-13	B細胞	IgEクラススイッチ促進
	インターフェロン	IFN-γ	B細胞	IgEクラススイッチ抑制
走化性サイトカイン(ケモカイン)	CCケモカイン	MIP-1	好中球	遊走
		MIP-2	好中球
		RANTES	単球
	CXCケモカイン	IL-8	好中球、リンパ球、好塩基球
	CXCケモカイン	SDF-1	好中球、リンパ球、好塩基球
造血系サイトカイン		SCF
	インターロイキン	IL-7
		erythropoietin
	コロニー刺激因子	GM-CSF
		G-CSF
		M-CSF

サイトカインのシグナル伝達 JAK/STAT pathway (IMM.245-246)

組み換えサイトカインと臨床利用 first aid step1 2006 p.327

agent		clinical uses
aldesleukin	interleukin-2	renal cell carcinoma, metastatic melanoma
erythropoietin	epoetin	anemias (especially in renal failure)
filgrastim	granulocyte colony-stimulating factor	recovery of bone marrow
sargramostim	granulocyte-macrophage colony stimulating factor	recovery of bone marrow
α-interferon		hepatitis B and C, Kaposi's sarcoma, leukemias, malignant melanoma
β-interferon		multiple sclerosis
γ-interferon		chronic granulomatous disease
oprelvekin	interleukin-11	thrombocytopenia
thrombopoietin		thrombocytopenia

「ホジキンリンパ腫」

　　[★]

英: Hodgkin's lymphoma Hodgkin lymphoma HL
同: Hodgkinリンパ腫、ホジキン病 (国試)Hodgkin病 Hodgkin disease Hodgkin's disease HD
関: 悪性リンパ腫

[show details]

ja

ホジキンリンパ腫 : 約 140,000 件
ホジキン病 : 約 77,800 件
Hodgkin's lymphoma : 約 14,000 件
Hodgkin lymphoma : 約 9,420 件
Hodgkin's disease : 約 7,570 件
Hodgkin disease : 約 2,760 件

en

Hodgkin's lymphoma : 約 1,210,000 件
Hodgkin lymphoma : 約 1,520,000 件
Hodgkin's disease : 約 737,000 件
Hodgkin disease : 約 794,000 件

概念

ホジキン細胞、リード・シュテルンベルグ細胞、および周囲に多彩な病理像を呈する炎症と局所リンパ節腫脹を伴うリンパ系腫瘍

疫学

日本では悪性リンパ腫の約10%を占める　⇔　欧米では30%程度。
好発年齢：若年者、中・高年者

病因

不明

病型

病理組織的な特徴から分類。

A. 結節性リンパ球優勢型
B. 古典型：ホジキン細胞の表面抗原(CD15+, CD20-, CD30+, CD45-)

1) 結節硬化型：高頻度
2) 混合細胞型：1)に次ぐが少ない。
3) リンパ球豊富型
4) リンパ球減少型

リンパ球減少型と混合細胞型はHIV感染患者によくみられる(HIM.699)

病期分類

参考2 YN.G-59

Ann Arbor 分類(Cotswolds 改訂)

I期	一リンパ節領域、またはリンパ組織(扁桃腺、脾臓、胸腺など)に病変が限局している場合。リンパ節以外の臓器の限局的なリンパ腫の病変がある場合。
II期	横隔膜を境界として、その上・下いずれか一方に限局した、二つ以上のリンパ節領域・リンパ組織の病変、もしくは一つのリンパ節領域・リンパ組織の病変と一つの非リンパ性臓器の浸潤
III期	横隔膜の両側に及ぶ、リンパ節領域・リンパ組織の病変
IV期	広汎な、リンパ節以外の臓器への浸潤