同: vascular cell adhesion molecule 1; CD106

インテグリン(VLA-1 integlin)と接着

同: CD106

同: vascular cell adhesion molecule 1

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/06/21 20:57:13」(JST)

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Vascular cell adhesion protein 1 also known as vascular cell adhesion molecule 1 (VCAM-1) or cluster of differentiation 106 (CD106) is a protein that in humans is encoded by the VCAM1 gene.^[1] VCAM-1 functions as a cell adhesion molecule.

Structure

The VCAM-1 gene contains six or seven immunoglobulin domains, and is expressed on both large and small blood vessels only after the endothelial cells are stimulated by cytokines. It is alternatively spliced into two known RNA transcripts that encode different isoforms in humans.^[2] The gene product is a cell surface sialoglycoprotein, a type I membrane protein that is a member of the Ig superfamily.

Function

The VCAM-1 protein mediates the adhesion of lymphocytes, monocytes, eosinophils, and basophils to vascular endothelium. It also functions in leukocyte-endothelial cell signal transduction, and it may play a role in the development of atherosclerosis and rheumatoid arthritis.

Upregulation of VCAM-1 in endothelial cells by cytokines occurs as a result of increased gene transcription (e.g., in response to Tumor necrosis factor-alpha (TNF-α) and Interleukin-1 (IL-1)) and through stabilization of Messenger RNA (mRNA) (e.g., Interleukin-4 (IL-4)). The promoter region of the VCAM-1 gene contains functional tandem NF-κB (nuclear factor-kappa B) sites. The sustained expression of VCAM-1 lasts over 24 hours.

Primarily, the VCAM-1 protein is an endothelial ligand for VLA-4 (Very Late Antigen-4 or α4β1) of the β1 subfamily of integrins, and for integrin α4β7. VCAM-1 expression has also been observed in other cell types (e.g., smooth muscle cells). It has also been shown to interact with EZR^[3] and Moesin.^[3]

Pharmacology

Certain melanoma cells can use VCAM-1 to adhere to the endothelium, and VCAM-1 may participate in monocyte recruitment to atherosclerotic sites. As a result, VCAM-1 is a potential drug target.

References

^ Cybulsky M, Fries JW, Williams AJ, Sultan P, Eddy RL, Byers MG, Shows TB, Gimbrone MA Jr, Collins T (1991). "The human VCAM1 gene is assigned to chromosome 1p31-p32". Cytogenet. Cell Genet. 58: 1852. DOI:10.1159/000133735.
^ "Entrez Gene: VCAM1 vascular cell adhesion molecule 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7412.
^ ^a ^b Barreiro, Olga; Yanez-Mo Maria, Serrador Juan M, Montoya Maria C, Vicente-Manzanares Miguel, Tejedor Reyes, Furthmayr Heinz, Sanchez-Madrid Francisco (Jun. 2002). "Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes". J. Cell Biol. (United States) 157 (7): 1233–45. DOI:10.1083/jcb.200112126. ISSN 0021-9525. PMC 2173557. PMID 12082081. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2173557.

External links

VCAM-1 at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 内皮：プライマー the endothelium a primer
2. 鎌状細胞貧血における臨床的ばらつき clinical variability in sickle cell anemia
3. 炎症の病因における白血球内皮細胞接着 leukocyte endothelial adhesion in the pathogenesis of inflammation
4. アテローム性動脈硬化症の病因 pathogenesis of atherosclerosis
5. 全身性硬化症（強皮症）の病因 pathogenesis of systemic sclerosis scleroderma

English Journal

MKP-7, a negative regulator of JNK, regulates VCAM-1 expression through IRF-1.

Nizamutdinova IT, Kim YM, Lee JH, Chang KC, Kim HJ.AbstractCell adhesion molecules (CAMs) are involved in a variety of pathologies including cancer, inflammation, pathogenic infections and autoimmune disease. In particular, VCAM-1, rather than ICAM-1, plays a major role in the initiation of atherosclerosis and tumor progression. Therefore, we attempted to elucidate differential mechanisms that regulate VCAM-1 and ICAM-1 expressions. Down-regulation of JNK by a specific inhibitor (SP600125) or dominant negative (DN) JNK1 plasmid enhanced TNF-α-induced VCAM-1 but not ICAM-1 expression. Moreover, transfection with a JNK1-overexpressing vector resulted in the inhibition of VCAM-1 expression stimulated by TNF-α in HUVECs, suggesting that JNK negatively regulates TNF-α-induced VCAM-1 expression in endothelial cells (ECs). Next, we investigated whether JNK signaling affects IRF-1 and/or GATA6, which are transcription factors that mediate TNF-α induction of VCAM-1 but not ICAM-1. The DN-JNK1 plasmid-transfected cells enhanced TNF-α up-regulation of IRF-1 whereas JNK1-overexpressing cells displayed down-regulation; however, neither DN-JNK1 transfection nor JNK1 overexpression affected GATA6 protein levels in the nuclear fraction. Chromatin immunoprecipitation (ChIP) assay confirmed that the inhibition of JNK by DN-JNK1 transfection increases the binding of IRF-1 to the VCAM-1 promoter whereas the overexpression of JNK1 inhibits IRF-1 binding to the VCAM-1 promoter. However, neither DN-JNK1 nor JNK1 overexpression altered GATA6 affinity for the VCAM-1 promoter region. We also examined whether MKP-7 affects ICAM-1 or VCAM-1 by regulating JNK. TNF-α-induced phosphor-JNK levels increased after 5min, peaked at 10min, and decreased after 30min. Interestingly, MKP-7 protein levels increased after 30min, when phosphor-JNK induction by TNF-α was decreased. In addition, silencing MKP-7 with specific siRNA resulted in an increase in phosphor-JNK and inhibited the expression of VCAM-1 but not ICAM-1. Moreover, silencing MKP-7 caused the down-regulation of IRF-1 protein levels and binding to the VCAM-1 promoter. Thus, we suggest that MKP-7, a negative regulator of JNK, regulates VCAM-1 expression in activated endothelial cells through IRF-1 but not GATA6.
Cellular signalling.Cell Signal.2012 Apr;24(4):866-72. Epub 2011 Dec 13.
Cell adhesion molecules (CAMs) are involved in a variety of pathologies including cancer, inflammation, pathogenic infections and autoimmune disease. In particular, VCAM-1, rather than ICAM-1, plays a major role in the initiation of atherosclerosis and tumor progression. Therefore, we attempted to e
PMID 22182512

Hepatocyte growth factor preferentially activates the anti-inflammatory arm of NF-κB signaling to induce A20 and protect renal proximal tubular epithelial cells from inflammation.

da Silva CG, Maccariello ER, Wilson SW, Putheti P, Daniel S, Damrauer SM, Peterson CR, Siracuse JJ, Kaczmarek E, Ferran C.SourceThe Division of Vascular Surgery, Department of Surgery, Center for Vascular Biology Research and the Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Journal of cellular physiology.J Cell Physiol.2012 Apr;227(4):1382-90. doi: 10.1002/jcp.22851.
Inflammation induces the NF-κB dependent protein A20 in human renal proximal tubular epithelial cells (RPTEC), which secondarily contains inflammation by shutting down NF-κB activation. We surmised that inducing A20 without engaging the pro-inflammatory arm of NF-κB could improve outcomes in kidn
PMID 21618526

Atherogenic alterations in hypertriglyceridemic patients would not depend on insulin resistance.

Gómez Rosso L, Meroño T, Giunta G, Boero L, Schreier L, Cuniberti L, Brites F.SourceLaboratory of Lipids of Lipoproteins, Department of Clinical Biochemistry, School of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, CONICET, Argentina.
Clinica chimica acta; international journal of clinical chemistry.Clin Chim Acta.2012 Mar 22;413(5-6):620-4. Epub 2011 Dec 16.
BACKGROUND AND AIMS: Several studies have been carried out to characterize the different alterations associated with hypertriglyceridemia (HTG) and to identify this dyslipemia as an independent risk factor for cardiovascular disease (CVD). HTG is frequently, but not always, associated with insulin r
PMID 22198537

Japanese Journal

細胞密度依存的なVCAM1の発現増加は間葉系幹細胞の遊走能を抑制する(岩手医科大学学位審査報告)

西平宗功
岩手医科大学歯学雑誌 36(2), 126-127, 2011-08-19
NAID 110008733449

好酸球性副鼻腔炎における好酸球浸潤の機序

大堀純一郎,黒野祐一
耳鼻咽喉科臨床 104(7), 465-473, 2011-07-01
… Two factors considered potentially related are (1) increased eosinophils infiltration from blood vessels into tissue and (2) eosinophil “pools” in tissue due to age. … During adherence in local eosinophil infiltration, vascular cell adhesion molecules (VCAM)-1 and alpha 4 beta 1 integrin (VLA-4) bind eosinophils selectivery. …
NAID 10029062670

F344/DUラット門脈遮断後の再灌流は脾臓皮膜下注入ACL-15大腸癌細胞の肝転移を促進させる

山本誠,麻沼和彦
信州医学雑誌 59(4), 249-257, 2011
… lecule-1 (VCAM-1),and intercellular adhesion molecule-1 (ICAM- 1)were determined 6 or 18 h after the first operation by quantitative RT-PCR for m-RNAs and immunohistochemical staining for proteins.Portal vein-clamped rats had significantly more liver metastatic foci than did unclamped controls.TPVC enhanced mRNA and protein expression of E-selectin,VCAM-1,and ICAM-1 on …
NAID 40018952424

Related Pictures

★リンクテーブル★

リンク元	「接着分子」「白血球」「T細胞」「血管細胞接着分子-1」「vascular cell adhesion molecule-1」
関連記事	「VCAM」「VC」「VCA」

「接着分子」

Vascular cell adhesion molecule 1
	; PDB rendering based on 1ij9.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1IJ9, 1VCA, 1VSC
Identifiers
Symbols	VCAM1; CD106; INCAM-100
External IDs	OMIM: 192225 MGI: 98926 HomoloGene: 838 ChEMBL: 3735 GeneCards: VCAM1 Gene
Gene Ontology
Molecular function	• integrin binding; • cell adhesion molecule binding; • cell adhesion molecule binding;
Cellular component	• podosome; • extracellular space; • plasma membrane; • microvillus; • external side of plasma membrane; • cell surface; • integral to membrane; • filopodium; • sarcolemma; • apical part of cell; • alpha9-beta1 integrin-vascular cell adhesion molecule-1 complex;
Biological process	• response to hypoxia; • acute inflammatory response; • chronic inflammatory response; • cell adhesion; • heterophilic cell-cell adhesion; • leukocyte cell-cell adhesion; • heart development; • aging; • response to nutrient; • response to ionizing radiation; • cytokine-mediated signaling pathway; • membrane to membrane docking; • B cell differentiation; • positive regulation of T cell proliferation; • interspecies interaction between organisms; • regulation of immune response; • leukocyte tethering or rolling; • interferon-gamma-mediated signaling pathway; • embryonic placenta morphogenesis; • chorio-allantoic fusion;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: adhesion molecule
同: 接着因子
関

接着分子のファミリー

インテグリンファミリー
Igスーパーファミリー
セレクチンファミリー
CD44ファミリー
カドヘリンファミリー

白血球の相互作用に関与している接着分子 (IMM.87)

グループ名	機能	名称	別名		組織分布	リガンド
セレクチン	炭化水素鎖に結合。白血球-内皮細胞の反応を開始	P-selectin	PADGEN	CD62P	活性化した内皮細胞、活性化した血小板	PSGL-1, sialyl-Lewisx
セレクチン	炭化水素鎖に結合。白血球-内皮細胞の反応を開始	E-selectin	ELAM-1	CD62E	活性化した内皮細胞	sialyl-Lewisx
インテグリン	CAMや細胞外マトリックスに結合。強い結合	LFA-1	αL:β2	CD11a:CD18	単球、T細胞、マクロファージ、好中球、樹状細胞	ICAMs
		CR3, Mac-1	αM:β2	CD11b:CD18	好中球、単球、マクロファージ	ICAM-1, iC3b, fibrinogen
		CR4, p150.95	αX:β2	CD11c:CD18	樹状細胞、マクロファージ、好中球	iC3b
		VLA-5	α5:β1	CD49d:CD29	単球、マクロファージ	fibronectin
免疫グロブリンスーパーファミリー	細胞結合で様々に働く。インテグリンの基質	ICAM-1		CD54	活性化した内皮細胞	LFA-1, MAC1
		ICAM-2		CD102	非活性化状態の内皮細胞、樹状細胞	LFA-1
		VCAM-1		CD106	活性化した内皮細胞	VLA-4
		PECAM		CD31	活性化した白血球、内皮細胞間の結合	CD31

白血球の相互作用に関与している免疫グロブリンスーパーファミリーの接着分子 (IMM.329)

名称		分布組織	リガンド
CD2	LFA-2	T細胞	LFA-1	CD53
ICAM-1	CD54	活性化した血管、リンパ球、樹状細胞	LFA-1, Mac-1
ICAM-2	CD102	非活性化状態の血管	LFA-1
ICAM-3	CD50	Naive T cells	DC-SIGN, LFA-1
LFA-3	CD58	リンパ球、APC	CD2
VCAM-1	CD106	活性化した内皮細胞	VLA-4

-接着分子

-細胞接着分子

-カドヘリン

「白血球」

　　[★]

英: leukocyte, leucocyte (Z), white blood cell (Z), WBC, white corpuscle, white cell
関: 赤血球、血球、血液

白血球

顆粒球

基準値

4000-9000 (/μl)　(2007前期解剖学授業プリント)

異常値の出るメカニズム第5版

5000- 8400 (/μl) (健常者の2/3)
4500-11000 (/μl) (95%範囲)

年齢との関連

新生児期>幼児期>成人期(20歳までに成人値)
妊婦でも増加(妊娠#妊娠による変化)

生理的な変動

精神的ストレス↑　　→　交感神経の刺激により好中球の血管壁遊離が促進されるため
午前↓、午後↑

基準値

			07解	異メ	流マ		HIM.A-1
顆粒球	好中球	桿状核球	40～70	44～66	40～60	4～14	0～5
		分葉核球				43～59	40～70
	好酸球		2～4	0～ 4	2～4		0～6
	好塩基球		0～2	0～0.5	0～2		0～2
無顆粒球	リンパ球		25～40	30～38	26～40		20～50
	単球		3～6	0～ 5	3～6		4～8

07解: 2007前期解剖学授業プリント
異メ: 異常値の出るメカニズム第5版 p.91
流マ: 流れが分かる実践検査マニュアル上巻 p.10

血管外滲出 extravasation (SMB.37 BPT.37)

(margination)

1. 赤血球は軽く早く流れるので血管の中央をながれ、白血球は血管のへりを流れている

(rolling)

2. IL-1, TNFで血管内皮細胞が活性化し、血管内腔にE-selectinを発現する
3. P-selectinはヒスタミンやトロンビンの働きにより、血管内腔に発現する
4. 白血球と血管内皮細胞の接着分子で接着することで、白血球がrollingを始める
3. 次第にselectinによる接着はdown regulateされる

(adheresion & arrested)

4. 炎症部位から出されたケモカインが血管内皮細胞の表面ののペプチドグリカンに結合し、白血球に提示される
5. 白血球表面のインテグリンが活性化し、血管内皮細胞のICAM-1, VCAM-1と強く結合する

(transmigration)

6. 白血球と血管内皮細胞に発現しているPECAM-1(CD31)がお互い接着し、白血球が血管内皮細胞の間隙を通って細胞外マトリックスに入る

血管内皮細胞		白血球
Rolling
E-selectin	－	糖鎖(SLe^x)
P-selectin	－	糖鎖
糖鎖(GlyCAM-1)(=CD34)	－	L-selectin
Adhestion
ICAM-1	－	LFA-1 integlin(CD11a/CD18), Mac-1 integlin(CD11b/CD18)
VCAM-1	－	VLA-1 integlin
transmigration
PECAM-1(CD31)	－	PECAM-1(CD31)

白血球の染色

ギムザ染色

好酸性：赤く染まる→ヘモグロビン
好塩基性：青く染まる→リボソーム、核内のヒストン蛋白
好酸性でも好塩基性でもない：淡いピンクに染まる

MPO myeloperoxidase反応（染色）

MPOをもつ：顆粒球（前骨髄球～分葉核球）、単球（前単球～単球）
MPOをもたない：リンパ球系細胞

エステラーゼ esterase

好中球：長鎖エステルを分解
単球：短鎖エステルを分解

関節液

　　炎症感染
200 2000 20000
500 5000 50000

臨床関連

LAD(leukocyte adhesion deficiency)症候群 (SMB.37)

白血球のインテグリンが欠損または減少する先天性疾患

反復性の細菌皮膚感染

SIRSの診断基準：＜4,000/ul or ＞12,000/ul

「T細胞」

　　[★]

英: T cell
同: Tリンパ球、T lymphocyte
関: TCR、B細胞、MHC

図：IMM.315(T細胞の成熟)
胸腺で成熟したT細胞は血流によって移動し、リンパ節の傍皮質、白脾髄のリンパ性動脈周囲鞘、パイエル板の傍濾胞域に集まる(人間の正常構造と機能 VIIA血管・免疫 p.28)

種類

T細胞の抗原認識 (SP.248)

	CD	TCRが抗原と共に認識する分子	認識する細胞
Tc細胞	CD8	MHCクラスI	感染細胞
Th細胞	CD4	MHCクラスII	抗原提示細胞

CD4+ T細胞のサイトカイン放出とその原因

DCが認識する外来異物	DCが分泌する物質	DCに反応する細胞	この細胞が分泌するサイトカイン	NK系の細胞が放出したサイトカインに反応するTh細胞	Th細胞が分泌するサイトカイン
ウイルス、一部の細菌	IL-12	NK細胞(IL-12による)	INF-γ	Th1	IL-2, IFN-γ, TNF-β
原虫など		NKT細胞	IL-4	Th2	IL-4, IL-13, IL-5

Th細胞活性化と接着分子

	抗原提示細胞	Th細胞
主シグナル	MHC classII	TCR, CD3
主シグナル	MHC classII	CD4
副シグナル	B7{B7-1(CD80)/B7-2(CD86)}	CD28
	VCAM-1(CD106)	VLA-4
	ICAM-1	LFA-1
	LFA-3(CD58)	CD2