インテグリン(CD11/CD18)(LFA-1 integlin(CD11a/CD18), Mac-1 integlin(CD11b/CD18)と接着

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/17 21:29:08」(JST)

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ICAM-1 (Intercellular Adhesion Molecule 1) also known as CD54 (Cluster of Differentiation 54) is a protein that in humans is encoded by the ICAM1 gene.^[1]^[2] This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by rhinovirus as a receptor.^[3]

Structure

ICAM-1 is a member of the immunoglobulin superfamily, the superfamily of proteins including antibodies and T-cell receptors. ICAM-1 is a transmembrane protein possessing an amino-terminus extracellular domain, a single transmembrane domain, and a carboxy-terminus cytoplasmic domain. The structure of ICAM-1 is characterized by heavy glycosylation, and the protein’s extracellular domain is composed of multiple loops created by disulfide bridges within the protein. The dominant secondary structure of the protein is the beta sheet, leading researchers to hypothesize the presence of dimerization domains within ICAM-1.^[4]

Function

The protein encoded by this gene is a type of intercellular adhesion molecule continuously present in low concentrations in the membranes of leukocytes and endothelial cells. Upon cytokine stimulation, the concentrations greatly increase. ICAM-1 can be induced by interleukin-1 (IL-1) and tumor necrosis factor (TNF) and is expressed by the vascular endothelium, macrophages, and lymphocytes. ICAM-1 is a ligand for LFA-1 (integrin), a receptor found on leukocytes.^[5] When activated, leukocytes bind to endothelial cells via ICAM-1/LFA-1 and then transmigrate into tissues.^[6]

Role in cell signaling

ICAM-1 (Intercellular Adhesion Molecule-1, CD54) is an endothelial- and leukocyte-associated transmembrane protein long known for its importance in stabilizing cell-cell interactions and facilitating leukocyte endothelial transmigration. More recently, ICAM-1 has been characterized as a site for the cellular entry of human rhinovirus.^[7] Because of these associations with immune responses, it has been hypothesized that ICAM-1 could function in signal transduction. ICAM-1 ligation produces proinflammatory effects such as inflammatory leukocyte recruitment by signaling through cascades involving a number of kinases, including the kinase p56lyn.

Other functions

ICAM-1 and soluble ICAM-1 have antagonistic effects on the tight junctions forming the blood-testis barrier, thus playing a major role in spermatogenesis.^[8]

The presence of heavy glycosylation and other structural characteristics of ICAM-1 lend the protein binding sites for numerous ligands. ICAM-1 possesses binding sites for a number of immune-associated ligands. Notably, ICAM-1 binds to macrophage adhesion ligand-1 (Mac-1; ITGB2 / ITGAM), leukocyte function associated antigen-1 (LFA-1), and fibrinogen. These three proteins are generally expressed on endothelial cells and leukocytes, and they bind to ICAM-1 to facilitate transmigration of leukocytes across vascular endothelia in processes such as extravasation and the inflammatory response. As a result of these binding characteristics, ICAM-1 has classically been assigned the function of intercellular adhesion.

Researchers began to question the role of ICAM-1 as a simple adhesion molecule upon discovering that ICAM-1 serves as the binding site for entry of the major group of human rhinovirus (HRV) into various cell types.^[4] ICAM-1 also became known for its affinity for plasmodium falciparum-infected erythrocytes (PFIE), providing more of a role for ICAM-1 in infectious disease.

With the roles of ICAM-1 in cell-cell adhesion, extravasation, and infection more fully understood, a potential role for ICAM-1 in signal transduction was hypothesized. Most of the work involving ICAM-1 in recent years has focused on this central question as well as related questions. Researchers reasoned that, should ICAM-1 signal transduction prove to occur, it would be necessary to identify the mechanism of that signaling, the conditions and environment in which the signaling would occur, and the biological endpoints of any signaling cascades involved. Beyond its classically described functions as an adhesion and viral entry molecule, ICAM-1 has now been characterized convincingly as possessing a role in signal transduction. Furthermore, the signal-transducing functions of ICAM-1 seem to be associated primarily with proinflammatory pathways. In particular, ICAM-1 signaling seems to produce a recruitment of inflammatory immune cells such as macrophages and granulocytes.^[9]

ICAM-1 may also participate in a positive-feedback loop and compete with ICAM-2 to maintain a proinflammatory environment conducive to leukocyte endothelial transmigration. At both the mRNA and protein levels of expression, ICAM-1 ligation was found to upregulate ICAM-1’s own expression in a positive-feedback loop. In addition, the expression of RANTES mRNA and protein was also found to be upregulated by ICAM-1 ligation. RANTES, or Regulated upon Activation Normal T-cell Expressed and Secreted, is a cytokine that is an inflammatory mediator chemotactic for a variety of inflammatory immune cells such as granulocytes and macrophages.^[10] However, much work remains to be done in fully characterizing the signaling of ICAM-1. The relationship between ICAM-1 and ICAM-2 signaling environments has not been established beyond mere correlation; a study linking ICAM signaling to actual modulation of an inflammatory environment in vivo has yet to be conducted. The reticular nature of signaling cascades necessitates that the downstream effectors of ICAM-1 mediated signaling through various kinases including p56lyn, Raf-1, and the MAPKs are largely unknown. A more thorough study of the cross-talk between these signaling molecules may shed further light onto the biological endpoints produced by ICAM-1 ligation and signal transduction.

Clinical significance

ICAM-1 has been implicated in subarachnoid hemorrhage (SAH). Levels of ICAM-1 are shown to be significantly elevated in patients with SAH over control subjects in many studies.^[11]^[12] While ICAM-1 has not been shown to be directly correlated with cerebral vasospasm, a secondary symptom that affects 70% of SAH patients, treatment with anti-ICAM-1 reduced the severity of vasospasm.

ICAM-1 expressed by respiratory epithelial cells is also the binding site for rhinovirus, the causative agent of most common colds.

ICAM-1 has an important role in ocular allergies recruiting pro-inflammatory lymphocytes and mast cells promoting a type I hypersensitivity reaction.

Interactions

ICAM-1 has been shown to interact with CD11a,^[13]^[14]^[15] EZR^[16] and CD18.^[13]^[17]^[18]

References

^ Carlson M, Nakamura Y, Payson R, O'Connell P, Leppert M, Lathrop GM, Lalouel JM, White R; Nakamura; Payson; O'Connell; Leppert; Lathrop; Lalouel; White (May 1988). "Isolation and mapping of a polymorphic DNA sequence (pMCT108.2) on chromosome 18 D18S24". Nucleic Acids Res. 16 (9): 4188. doi:10.1093/nar/16.9.4188. PMC 336612. PMID 2453850.
^ Katz FE, Parkar M, Stanley K, Murray LJ, Clark EA, Greaves MF; Parkar; Stanley; Murray; Clark; Greaves (January 1985). "Chromosome mapping of cell membrane antigens expressed on activated B cells". Eur. J. Immunol. 15 (1): 103–6. doi:10.1002/eji.1830150121. PMID 3871395.
^ "Entrez Gene: intercellular adhesion molecule 1".
^ ^a ^b Bella J, Kolatkar PR, Marlor CW, Greve JM, Rossmann MG; Kolatkar; Marlor; Greve; Rossmann (April 1998). "The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand". Proc. Natl. Acad. Sci. U.S.A. 95 (8): 4140–5. doi:10.1073/pnas.95.8.4140. PMC 22455. PMID 9539703.
^ Rothlein, R. D.; Dustin, M. L.; Marlin, S. D.; Springer, T. A. (Aug 1986). "A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1". Journal of Immunology 137 (4): 1270–1274. ISSN 0022-1767. PMID 3525675. edit
^ Yang L, Froio RM, Sciuto TE, Dvorak AM, Alon R, Luscinskas FW; Froio; Sciuto; Dvorak; Alon; Luscinskas (July 2005). "ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-α-activated vascular endothelium under flow". Blood 106 (2): 584–92. doi:10.1182/blood-2004-12-4942. PMC 1635241. PMID 15811956.
^ Abraham G, Colonno RJ; Colonno (August 1984). "Many rhinovirus serotypes share the same cellular receptor". J. Virol. 51 (2): 340–5. PMC 254443. PMID 6086949.
^ Xiao, X.; Mruk, D. D.; Cheng, C. Y. (2013). "Intercellular adhesion molecules (ICAMs) and spermatogenesis". Human Reproduction Update 19 (2): 167–186. doi:10.1093/humupd/dms049. PMC 3576004. PMID 23287428. edit
^ Etienne-Manneville S, Chaverot N, Strosberg AD, Couraud PO; Chaverot; Strosberg; Couraud (July 1999). "ICAM-1-coupled signaling pathways in astrocytes converge to cyclic AMP response element-binding protein phosphorylation and TNF-alpha secretion". J. Immunol. 163 (2): 668–74. PMID 10395656.
^ Blaber R, Stylianou E, Clayton A, Steadman R; Stylianou; Clayton; Steadman (January 2003). "Selective regulation of ICAM-1 and RANTES gene expression after ICAM-1 ligation on human renal fibroblasts". J. Am. Soc. Nephrol. 14 (1): 116–27. doi:10.1097/01.ASN.0000040595.35207.62. PMID 12506144.
^ Polin RS, Bavbek M, Shaffrey ME, Billups K, Bogaev CA, Kassell NF, Lee KS; Bavbek; Shaffrey; Billups; Bogaev; Kassell; Lee (October 1998). "Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage". J. Neurosurg. 89 (4): 559–67. doi:10.3171/jns.1998.89.4.0559. PMID 9761049.
^ Frijns CJ, Kappelle LJ; Kappelle (August 2002). "Inflammatory cell adhesion molecules in ischemic cerebrovascular disease". Stroke 33 (8): 2115–22. doi:10.1161/01.STR.0000021902.33129.69. PMID 12154274.
^ ^a ^b Lu, C; Springer T A (May 2001). "Association of the membrane proximal regions of the alpha and beta subunit cytoplasmic domains constrains an integrin in the inactive state". J. Biol. Chem. (United States) 276 (18): 14642–8. doi:10.1074/jbc.M100600200. ISSN 0021-9258. PMID 11279101.
^ Shimaoka, Motomu; Springer Timothy A (Jan 2003). "Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation". Cell (United States) 112 (1): 99–111. doi:10.1016/S0092-8674(02)01257-6. ISSN 0092-8674. PMID 12526797.
^ Yusuf-Makagiansar, H; Makagiansar I T; Hu Y; Siahaan T J (Dec 2001). "Synergistic inhibitory activity of alpha- and beta-LFA-1 peptides on LFA-1/ICAM-1 interaction". Peptides (United States) 22 (12): 1955–62. doi:10.1016/S0196-9781(01)00546-0. ISSN 0196-9781. PMID 11786177.
^ Heiska, L; Alfthan K; Grönholm M; Vilja P; Vaheri A; Carpén O (Aug 1998). "Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol 4, 5-bisphosphate". J. Biol. Chem. (UNITED STATES) 273 (34): 21893–900. doi:10.1074/jbc.273.34.21893. ISSN 0021-9258. PMID 9705328.
^ Kotovuori, A; Pessa-Morikawa T; Kotovuori P; Nortamo P; Gahmberg C G (Jun 1999). "ICAM-2 and a peptide from its binding domain are efficient activators of leukocyte adhesion and integrin affinity". J. Immunol. (UNITED STATES) 162 (11): 6613–20. ISSN 0022-1767. PMID 10352278.
^ Huang, C; Springer T A (Aug 1995). "A binding interface on the I domain of lymphocyte function-associated antigen-1 (LFA-1) required for specific interaction with intercellular adhesion molecule 1 (ICAM-1)". J. Biol. Chem. (UNITED STATES) 270 (32): 19008–16. doi:10.1074/jbc.270.32.19008. ISSN 0021-9258. PMID 7642561.

External links

Intercellular Adhesion Molecule-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. 臨床的腎移植における研究中の免疫抑制剤およびそのアプローチ investigational immunosuppressive drugs and approaches in clinical kidney transplantation
2. クローン病の内科的マネージメントにおける試験研究治療 investigational therapies in the medical management of crohn disease
3. ライノウイルス感染の疫学、臨床症状、および病因 epidemiology clinical manifestations and pathogenesis of rhinovirus infections
4. Leukocyte-adhesion deficiency
5. 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

English Journal

High-intensity exercise attenuates postprandial lipaemia and markers of oxidative stress.

Gabriel B, Ratkevicius A, Gray P, Frenneaux MP, Gray SR.SourceInstitute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Clinical science (London, England : 1979).Clin Sci (Lond).2012 Sep;123(5):313-21.
Regular exercise can reduce the risk of CVD (cardiovascular disease). Although moderate-intensity exercise can attenuate postprandial TAG (triacylglycerol), high-intensity intermittent exercise might be a more effective method to improve health. We compared the effects of high-intensity intermittent
PMID 22435779

Depletion of protein kinase N3 (PKN3) impairs actin and adherens junctions dynamics and attenuates endothelial cell activation.

Möpert K, Löffler K, Röder N, Kaufmann J, Santel A.SourceSilence Therapeutics AG, 13125 Berlin, Germany.
European journal of cell biology.Eur J Cell Biol.2012 Sep;91(9):694-705. Epub 2012 May 19.
Several pathways are involved in the control of endothelial cell morphology, endothelial permeability and function in order to maintain vascular homeostasis. Here we report that protein kinase N3 (PKN3) appears to play a pivotal role in maintaining endothelial cell morphology, cell-cell junctions an
PMID 22609186

TNFα affects energy metabolism and stimulates biogenesis of mitochondria in EA.hy926 endothelial cells.

Drabarek B, Dymkowska D, Szczepanowska J, Zabłocki K.SourceNencki Institute of Experimental Biology PAS, 3 Pasteur Str., 02-093 Warsaw, Poland.
The international journal of biochemistry & cell biology.Int J Biochem Cell Biol.2012 Sep;44(9):1390-7. Epub 2012 Jun 9.
Mitochondrial response of EA.hy926 endothelial cells to tumour necrosis factor alpha (TNFα) was investigated. It was confirmed that TNFα stimulates reactive oxygen species (ROS) generation and increases intercellular adhesion molecule-1 (ICAM-1) level. These changes were paralleled by elevated oxy
PMID 22687752

Japanese Journal

Atherosclerotic plaques induced by marble-burying behavior are stabilized by exercise training in experimental atherosclerosis.

Shimada Kana,Mikami Yu,Murayama Toshinori,Yokode Masayuki,Fujita Masatoshi,Kita Toru,Kishimoto Chiharu
International journal of cardiology 151(3), 284-289, 2011-09-15
… The plaques containing macrophage accumulation with intercellular adhesion molecule-1 (ICAM-1) expression associated with reduced collagen contents were induced in the mice treated with marble-burying. … However, ICAM-1 expression was suppressed and collagen contents were reversed in the mice that received marble-burying behavior plus exercise training. …
NAID 120003405530

Involvement of MAPKs in ICAM-1 Expression in Glomerular Endothelial Cells in Diabetic Nephropathy

Watanabe Naomi,Shikata Kenichi,Shikata Yasushi,Sarai Kei,Omori Kazuyoshi,Kodera Ryo,Sato Chikage,Wada Jun,Makino Hirofumi
Acta Medica Okayama 65(4), 247-257, 2011-08
… The aim of this study was to clarify the role of mitogen-activated protein kinase (MAPK) pathways for induction of intercellular adhesion molecule-1 (ICAM-1) expression in glomerular endothelial cells under diabetic conditions. … We examined the expression of ICAM-1 in the kidneys of experimental diabetic rats. …
NAID 80021895207

Radiation-induced ICAM-1 Expression via TGF-β1 Pathway on Human Umbilical Vein Endothelial Cells ; Comparison between X-ray and Carbon-ion Beam Irradiation

KIYOHARA Hiroki,ISHIZAKI Yasuki,SUZUKI Yoshiyuki,KATOH Hiroyuki,HAMADA Nobuyuki,OHNO Tatsuya,TAKAHASHI Takeo,KOBAYASHI Yasuhiko,NAKANO Takashi
Journal of radiation research 52(3), 287-292, 2011-05-16
… Intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta1 (TGF-β1) are thought to play important roles in this process. … In this study, radiation-induced ICAM-1 expression on endothelial cells was investigated with the use of an inhibitor of TGF-β1 receptor kinase (SB431542) and the effects of X-ray and carbon-ion beam were compared. …
NAID 10028111131

Related Pictures

★リンクテーブル★

リンク元	「接着分子」「白血球」「T細胞」「キラーT細胞」「インテグリン」
関連記事	「IC」「ICAM」「ICA」

「接着分子」

Intercellular adhesion molecule 1
	PDB rendering based on 1d3e.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1D3E, 1D3I, 1D3L, 1IAM, 1IC1, 1IJ4, 1MQ8, 1P53, 1Z7Z, 2OZ4, 3TCX
Identifiers
Symbols	ICAM1 ; BB2; CD54; P3.58
External IDs	OMIM: 147840 MGI: 96392 HomoloGene: 168 ChEMBL: 3070 GeneCards: ICAM1 Gene
Gene ontology
Molecular function	• virus receptor activity; • receptor activity; • transmembrane signaling receptor activity; • integrin binding; • protein binding;
Cellular component	• immunological synapse; • extracellular space; • plasma membrane; • integral component of plasma membrane; • focal adhesion; • external side of plasma membrane; • cell surface; • membrane; • membrane raft; • extracellular exosome;
Biological process	• ovarian follicle development; • regulation of leukocyte mediated cytotoxicity; • response to amphetamine; • T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell; • acute inflammatory response to antigenic stimulus; • T cell antigen processing and presentation; • positive regulation of cellular extravasation; • cell adhesion; • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; • leukocyte cell-cell adhesion; • cell aging; • sensory perception of sound; • regulation of cell shape; • response to ionizing radiation; • response to sulfur dioxide; • response to organic cyclic compound; • cytokine-mediated signaling pathway; • membrane to membrane docking; • regulation of cell adhesion; • extracellular matrix organization; • positive regulation of actin filament polymerization; • cellular response to nutrient levels; • cell adhesion mediated by integrin; • response to gonadotropin; • response to drug; • response to amino acid; • positive regulation of GTPase activity; • adhesion of symbiont to host; • positive regulation of nitric oxide biosynthetic process; • response to ethanol; • positive regulation of vasoconstriction; • response to copper ion; • viral entry into host cell; • receptor-mediated virion attachment to host cell; • positive regulation of peptidyl-tyrosine phosphorylation; • regulation of immune response; • leukocyte migration; • positive regulation of NF-kappaB transcription factor activity; • negative regulation of calcium ion transport; • interferon-gamma-mediated signaling pathway; • establishment of endothelial barrier; • positive regulation of ERK1 and ERK2 cascade; • cellular response to lipopolysaccharide; • cellular response to alkaloid; • cellular response to glucose stimulus; • cellular response to interleukin-1; • cellular response to tumor necrosis factor; • cellular response to hypoxia; • establishment of Sertoli cell barrier; • regulation of ruffle assembly; • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; • negative regulation of endothelial cell apoptotic process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

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

「キラーT細胞」

　　[★]

英: killer T cell
同: 細胞傷害性T細胞 cytotoxic T cell 、細胞溶解性T細胞 cytolytic T cell、細胞傷害性Tリンパ球 cytotoxic T lymphocyte CTL、細胞溶解性Tリンパ球 cytolytic T lymphocyte CTL
関: ヘルパーT細胞、T細胞、ラック細胞 LAK細胞

同: KT

偏性細胞内寄生体であるウイルス感染において特に誘導されやすい (SMB.47)

機能

キラーT細胞のTCRが、抗原を提示しているMHC class Iを認識し、キラーT細胞のCD8がMHC class Iとの結合を増強して、細胞傷害を行う (SP.250)
攻撃の方法は２つあり、リソソームから酵素を注入する方法と、パーフォリン(perforin)を注入する方法とがある (SP.250)

抗原認識と細胞傷害 (SMB.48)

1. キラーT細胞のTCRがが抗原を提示したMHC class Iを認識
2. CD8がMHC class Iに結合
3. キラーT細胞で発現しているLFA-1が標的細胞のICAM-1と結合
4. キラーT細胞がFasリガンドを発現し、標的細胞のFasに結合
5. パーフォリンが放出される
6. グランザイムが注入される

新しいトピック

グラニュライシン, granulysin (SMB.48)

結核菌の殺傷に関与

-細胞傷害性T細胞

「インテグリン」

　　[★]

英: integrin, integrins
関

インテグリン IMM.87

name			tissue distribution					ligand
name			単球	T細胞	マクロファージ	好中球	樹状細胞	ligand
αL:β2	LFA-1	CD11a:CD18	○	○	○	○	○	ICAMs
αM:β2	CR3, Mac-1	CD11b:CD18	○		○	○		ICAM-1, iC3b, fibrinogen
αｘ:β2	CR4, p150.90	CD11c:CD18			○	○	○	iC3b
α5:β1	VLA-5	CD49d:CD29	○		○			fibronectin

「IC」

　　[★]

「ICAM」

　　[★]

同: intercellular adhesion molecule

いずれもβ₂インテグリンの LFA-1と結合

種類

関: adhesion molecules, intercellular

「ICA」

　　[★]

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[pmid3871395-2] Katz FE, Parkar M, Stanley K, Murray LJ, Clark EA, Greaves MF; Parkar; Stanley; Murray; Clark; Greaves (January 1985). "Chromosome mapping of cell membrane antigens expressed on activated B cells". Eur. J. Immunol. 15 (1): 103–6. doi:10.1002/eji.1830150121. PMID 3871395.

[entrez-3] "Entrez Gene: intercellular adhesion molecule 1".

[pmid9539703-4] Bella J, Kolatkar PR, Marlor CW, Greve JM, Rossmann MG; Kolatkar; Marlor; Greve; Rossmann (April 1998). "The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand". Proc. Natl. Acad. Sci. U.S.A. 95 (8): 4140–5. doi:10.1073/pnas.95.8.4140. PMC 22455. PMID 9539703.

[5] Rothlein, R. D.; Dustin, M. L.; Marlin, S. D.; Springer, T. A. (Aug 1986). "A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1". Journal of Immunology 137 (4): 1270–1274. ISSN 0022-1767. PMID 3525675. edit

[pmid15811956-6] Yang L, Froio RM, Sciuto TE, Dvorak AM, Alon R, Luscinskas FW; Froio; Sciuto; Dvorak; Alon; Luscinskas (July 2005). "ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-α-activated vascular endothelium under flow". Blood 106 (2): 584–92. doi:10.1182/blood-2004-12-4942. PMC 1635241. PMID 15811956.

[pmid6086949-7] Abraham G, Colonno RJ; Colonno (August 1984). "Many rhinovirus serotypes share the same cellular receptor". J. Virol. 51 (2): 340–5. PMC 254443. PMID 6086949.

[xiao2013-8] Xiao, X.; Mruk, D. D.; Cheng, C. Y. (2013). "Intercellular adhesion molecules (ICAMs) and spermatogenesis". Human Reproduction Update 19 (2): 167–186. doi:10.1093/humupd/dms049. PMC 3576004. PMID 23287428. edit

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[pmid12506144-10] Blaber R, Stylianou E, Clayton A, Steadman R; Stylianou; Clayton; Steadman (January 2003). "Selective regulation of ICAM-1 and RANTES gene expression after ICAM-1 ligation on human renal fibroblasts". J. Am. Soc. Nephrol. 14 (1): 116–27. doi:10.1097/01.ASN.0000040595.35207.62. PMID 12506144.

[pmid9761049-11] Polin RS, Bavbek M, Shaffrey ME, Billups K, Bogaev CA, Kassell NF, Lee KS; Bavbek; Shaffrey; Billups; Bogaev; Kassell; Lee (October 1998). "Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage". J. Neurosurg. 89 (4): 559–67. doi:10.3171/jns.1998.89.4.0559. PMID 9761049.

[pmid12154274-12] Frijns CJ, Kappelle LJ; Kappelle (August 2002). "Inflammatory cell adhesion molecules in ischemic cerebrovascular disease". Stroke 33 (8): 2115–22. doi:10.1161/01.STR.0000021902.33129.69. PMID 12154274.

[pmid11279101-13] Lu, C; Springer T A (May 2001). "Association of the membrane proximal regions of the alpha and beta subunit cytoplasmic domains constrains an integrin in the inactive state". J. Biol. Chem. (United States) 276 (18): 14642–8. doi:10.1074/jbc.M100600200. ISSN 0021-9258. PMID 11279101.

[pmid12526797-14] Shimaoka, Motomu; Springer Timothy A (Jan 2003). "Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation". Cell (United States) 112 (1): 99–111. doi:10.1016/S0092-8674(02)01257-6. ISSN 0092-8674. PMID 12526797.

[pmid11786177-15] Yusuf-Makagiansar, H; Makagiansar I T; Hu Y; Siahaan T J (Dec 2001). "Synergistic inhibitory activity of alpha- and beta-LFA-1 peptides on LFA-1/ICAM-1 interaction". Peptides (United States) 22 (12): 1955–62. doi:10.1016/S0196-9781(01)00546-0. ISSN 0196-9781. PMID 11786177.

[pmid9705328-16] Heiska, L; Alfthan K; Grönholm M; Vilja P; Vaheri A; Carpén O (Aug 1998). "Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol 4, 5-bisphosphate". J. Biol. Chem. (UNITED STATES) 273 (34): 21893–900. doi:10.1074/jbc.273.34.21893. ISSN 0021-9258. PMID 9705328.

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[pmid7642561-18] Huang, C; Springer T A (Aug 1995). "A binding interface on the I domain of lymphocyte function-associated antigen-1 (LFA-1) required for specific interaction with intercellular adhesion molecule 1 (ICAM-1)". J. Biol. Chem. (UNITED STATES) 270 (32): 19008–16. doi:10.1074/jbc.270.32.19008. ISSN 0021-9258. PMID 7642561.

匿名

検索

案内

ICAM-1