WordNet

a protein present in blood plasma; converts to fibrin when blood clots (同)factor_I
a rare congenital disorder of blood coagulation in which no fibrinogen is found in the blood plasma

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/05/26 23:08:38」(JST)

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Fibrinogen alpha/beta chain family

crystal structure of native chicken fibrinogen with two different bound ligands

Identifiers

Symbol

Fib_alpha

Pfam

PF08702

InterPro

IPR012290

SCOP

1m1j

SUPERFAMILY

1m1j

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

Fibrinogen alpha C domain

Identifiers

Symbol

Fibrinogen_aC

Pfam

PF12160

InterPro

IPR021996

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

Fibrinogen beta and gamma chains, C-terminal globular domain

crystal structure of native chicken fibrinogen with two different bound ligands

Identifiers

Symbol

Fibrinogen_C

Pfam

PF00147

Pfam clan

CL0422

InterPro

IPR002181

PROSITE

PDOC00445

SCOP

1fza

SUPERFAMILY

1fza

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

Fibrinogen (factor I) consists of a linear array of 3 nodules held together by a very thin thread which is estimated to have a diameter of from 8 to 15 A. The two end nodules are alike but the center one is slightly smaller. Measurements of shadow lengths indicate that nodule diameters are in the range 50 to 70 A. The length of the dried molecule is 475 =t= 25 A.^[2]

The Fibrinogen molecule is a soluble, large, and complex glycoprotein, 340 kDa plasma glycoprotein, that is converted by thrombin into fibrin during blood clot formation. It has a rod-like shape with dimensions of 9 x 47.5 x 6nm and it shows a negative net charge at physiological pH (IP at pH 5.2).^[3] Fibrinogen is synthesized in the liver by the hepatocytes.^[3] The concentration of fibrinogen in the blood plasma is 200–400 mg/dL (normally measured using the Clauss method).

During normal blood coagulation, a coagulation cascade activates the zymogen prothrombin by converting it into the serine protease thrombin. Thrombin then converts the soluble fibrinogen into insoluble fibrin strands. These strands are then cross-linked by factor XIII to form a blood clot. FXIIa stabilizes fibrin further by incorporation of the fibrinolysis inhibitors alpha-2-antiplasmin and TAFI (thrombin activatable fibrinolysis inhibitor, procarboxypeptidase B), and binding to several adhesive proteins of various cells.^[4] Both the activation of Factor XIII by thrombin and plasminogen activator (t-PA) are catalyzed by fibrin.^[4] Fibrin specifically binds the activated coagulation factors factor Xa and thrombin and entraps them in the network of fibers, thus functioning as a temporary inhibitor of these enzymes, which stay active and can be released during fibrinolysis.^[5] Recent research has shown that fibrin plays a key role in the inflammatory response and development of rheumatoid arthritis.^[6]^{[citation needed]}

Physiology

In its natural form, fibrinogen can form bridges between platelets, by binding to their GpIIb/IIIa surface membrane proteins; however, its major function is as the precursor to fibrin.

Fibrinogen, the principal protein of vertebrate blood clotting, is a hexamer, containing two sets of three different chains (α, β, and γ), linked to each other by disulfide bonds. The N-terminal sections of these three chains contain the cysteines that participate in the cross-linking of the chains. The C-terminal parts of the α, β and γ chains contain a domain of about 225 amino-acid residues, which can function as a molecular recognition unit. In fibrinogen as well as in angiopoietin, this domain is implicated in protein-protein interactions. In lectins, such as mammalian ficolins and invertebrate tachylectin 5A, the fibrinogen C-terminal domain binds carbohydrates. On the fibrinogen α and β chains, there is a small peptide sequence (called a fibrinopeptide). These small peptides are what prevent fibrinogen from spontaneously forming polymers with itself.^[7]

The conversion of fibrinogen to fibrin occurs in several steps. First, thrombin cleaves the N-terminus of the fibrinogen alpha and beta chains to fibrinopeptide A and B respectively.^[8] The resulting fibrin monomers polymerize end to end to from protofibrils, which in turn associate laterally to form fibrin fibers.^[9] In a final step, the fibrin fibers associate to form the fibrin gel.^[10]

Fibrinogen deficiency

Congenital fibrinogen deficiency (afibrinogenemia) or disturbed function of fibrinogen has been described in a few cases.^[11]

It can lead to either bleeding or thromboembolic complications, or is clinically without pathological findings. More common are acquired deficiency stages that can be detected by laboratory tests in blood plasma or in whole blood by means of thrombelastometry.^[12] Acquired deficiency is found after hemodilution, blood losses and/or consumption such as in trauma patients, during some phases of disseminated intravascular coagulation (DIC), and also in sepsis. In patients with fibrinogen deficiency, the correction of bleeding is possible by infusion of fresh frozen plasma (FFP), cryoprecipitate (a fibrinogen-rich plasma fraction) or by fibrinogen concentrates. There is increasing evidence that correction of fibrinogen deficiency or fibrinogen polymerization disorders is very important in patients with bleeding.^[13]

Diagnostic use

Fibrinogen levels can be measured in venous blood. Normal levels are about 1.5-3 g/L, depending on the method used. In typical circumstances, fibrinogen is measured in citrated plasma samples in the laboratory, however the analysis of whole-blood samples by use of thromboelastometry (platelet function is inhibited with cytochalasin D) is also possible.^[12] Higher levels are, amongst others, associated with cardiovascular disease (>3.43 g/L). It may be elevated in any form of inflammation, as it is an acute-phase protein; for example, it is especially apparent in human gingival tissue during the initial phase of periodontal disease.^[14] Fibrinogen levels increase in pregnancy to an average of 4.5 g/l, compared to an average of 3 g/l in non-pregnant people.^[15]

It is used in veterinary medicine as an inflammatory marker: In horses, a level above the normal range of 1.0-4.0 g/L suggests some degree of systemic inflammatory response.^{[citation needed]}

Low levels of fibrinogen can indicate a systemic activation of the clotting system, with consumption of clotting factors faster than synthesis. This excessive clotting factor consumption condition is known as disseminated intravascular coagulation or "DIC." DIC can be difficult to diagnose, but a strong clue is low fibrinogen levels in the setting of prolonged clotting times (PT or aPTT), in the context of acute critical illness such as sepsis or trauma. Besides low fibrinogen level, fibrin polymerization disorders that can be induced by several factors, including plasma expanders, can also lead to severe bleeding problems.^[12] Fibrin polymerization disorders can be detected by viscoelastic methods such as thrombelastometry.^[12]

References

^ PDB 1FZC; Everse SJ, Spraggon G, Veerapandian L, Riley M, Doolittle RF (June 1998). "Crystal structure of fragment double-D from human fibrin with two different bound ligands". Biochemistry 37 (24): 8637–42. doi:10.1021/bi9804129. PMID 9628725.
^ Hall, Ph.D., Cecil E.; HENRY S. SLAYTER (18 August 1958). "The Fibrinogen Molecule: Its Size, Shape, and Mode of Polymerization". The Journal of Biophysical and Biochemical Cytology. Plate 1 (in English) (Cambridge, M: e Department of Biology, Massachusetts Institute of Technology). Volume 5. Retrieved 24 May 2014. Cite uses deprecated parameters (help)
^ ^a ^b Marucco, Arianna; et al (2013). "Interaction of fibrinogen and albumin with titanium dioxide nanoparticles of different crystalline phases". Journal of Physics. Conference Series 429 (Issue 1). Retrieved 24 May 2014. Cite uses deprecated parameters (help)
^ ^a ^b Muszbek L, Bagoly Z, Bereczky Z, Katona E (July 2008). "The involvement of blood coagulation factor XIII in fibrinolysis and thrombosis". Cardiovascular & Hematological Agents in Medicinal Chemistry 6 (3): 190–205. doi:10.2174/187152508784871990. PMID 18673233.
^ Kaiser B (2003). "DX-9065a, a direct inhibitor of factor Xa". Cardiovascular Drug Reviews 21 (2): 91–104. doi:10.1111/j.1527-3466.2003.tb00108.x. PMID 12847561.
^ Gilliam BE; Reed, Melinda R; Chauhan, Anil K; Dehlendorf, Amanda B; Moore, Terry L (2011). "Evidence of Fibrinogen as a Target of Citrullination in IgM Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis". Pediatric Rheumatology 9 (8): xx–xx. doi:10.1186/1546-0096-9-8. ISSN 1546-0096. PMC 3071779. PMID 21439056.
^ PDOC00445 Fibrinogen C-terminal domain in PROSITE
^ Blombäck B, Hessel B, Hogg D, Therkildsen L (October 1978). "A two-step fibrinogen--fibrin transition in blood coagulation". Nature 275 (5680): 501–5. doi:10.1038/275501a0. PMID 692730.
^ Hermans J, McDonagh J (January 1982). "Fibrin: structure and interactions". Semin. Thromb. Hemost. 8 (1): 11–24. doi:10.1055/s-2007-1005039. PMID 7036348.
^ Lorand L, Credo RB; John W. Fenton; Kenneth G. Mann (1977). "hrombin and fibrin stabilization". In Mann KG, Lundblad RL, Fenton J. Chemistry and Biology of Thrombin. Ann Arbor, Mich: Ann Arbor Science Publishers. pp. 311–323. ISBN 0-250-40160-6.
^ Acharya SS, Dimichele DM (November 2008). "Rare inherited disorders of fibrinogen". Haemophilia : the Official Journal of the World Federation of Hemophilia 14 (6): 1151–8. doi:10.1111/j.1365-2516.2008.01831.x. PMID 19141154.
^ ^a ^b ^c ^d Lang T, Johanning K, Metzler H, Piepenbrock S, Solomon C, Rahe-Meyer N, Tanaka KA (March 2009). "The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia". Anesthesia and Analgesia 108 (3): 751–8. doi:10.1213/ane.0b013e3181966675. PMID 19224779.
^ Fries D, Innerhofer P, Schobersberger W (April 2009). "Time for changing coagulation management in trauma-related massive bleeding". Current Opinion in Anaesthesiology 22 (2): 267–74. doi:10.1097/ACO.0b013e32832678d9. PMID 19390253.
^ Page RC, Schroeder HE (March 1976). "Pathogenesis of inflammatory periodontal disease. A summary of current work". Lab. Invest. 34 (3): 235–49. PMID 765622.
^ Salvi, Vinita (2003). Medical and Surgical Diagnostic Disorders in Pregnancy. Jaypee Brothers Publishers. p. 5. ISBN 978-81-8061-090-5.

External links

Jennifer McDowall/Interpro: Protein Of The Month: Fibrinogen.
D'Eustachio/reactome: fibrinogen → fibrin monomer + 2 fibrinopeptide A + 2 fibrinopeptide B

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. フィブリノゲンの異常 disorders of fibrinogen
2. 出血性素因を有する成人患者へのアプローチ approach to the adult patient with a bleeding diathesis
3. 凝固検査の臨床使用 clinical use of coagulation tests
4. 成人における確定診断を得られていない低血圧やショックの評価および初期アプローチ evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock
5. 出血症状を有する小児に対するアプローチ approach to the child with bleeding symptoms

English Journal

The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates.

Lewis JS, Dolgova NV, Chancellor TJ, Acharya AP, Karpiak JV, Lele TP, Keselowsky BG.SourceJ. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA.
Biomaterials.Biomaterials.2013 Dec;34(36):9063-70. doi: 10.1016/j.biomaterials.2013.08.021. Epub 2013 Sep 3.
Dendritic cells (DCs), key regulators of tolerance and immunity, have been found to reside in mechanically active tissues such as the interior layers of the arterial wall, which experience cyclic radial wall strain due to pulsatile blood flow. Although experimentally difficult to determine in vivo,
PMID 24008042

Enhanced infarct stabilization and neovascularization mediated by VEGF-loaded PEGylated fibrinogen hydrogel in a rodent myocardial infarction model.

Rufaihah AJ, Vaibavi SR, Plotkin M, Shen J, Nithya V, Wang J, Seliktar D, Kofidis T.SourceDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: surraj@nus.edu.sg.
Biomaterials.Biomaterials.2013 Nov;34(33):8195-202. doi: 10.1016/j.biomaterials.2013.07.031. Epub 2013 Jul 24.
Most tissue engineering therapies require biomaterials that are able to induce an angiogenic response to support tissue regeneration. In addition angiogenic growth factor signaling plays an essential role in controlling the process of angiogenesis and matrices have the potential of regulating the co
PMID 23891519

Partial recovery of the damaged rat blood-brain barrier is mediated by adherens junction complexes, extracellular matrix remodeling and macrophage infiltration following focal astrocyte loss.

Willis CL, Camire RB, Brule SA, Ray DE.SourceDepartment of Biomedical Sciences, College of Osteopathic Medicine, University of New England, 11 Hills Beach Road, Biddeford, ME 04005, USA. Electronic address: cwillis1@une.edu.
Neuroscience.Neuroscience.2013 Oct 10;250:773-85. doi: 10.1016/j.neuroscience.2013.06.061. Epub 2013 Jul 9.
Blood-brain barrier (BBB) dysfunction is a feature of many neurodegenerative disorders. The mechanisms and interactions between astrocytes, extracellular matrix and vascular endothelial cells in regulating the mature BBB are poorly understood. We have previously shown that transitory glial fibrillar
PMID 23845748

Japanese Journal

Pharmacology: Comparison of the blood coagulation profiles of ferrets and rats

Takahashi Saya,Hirai Norihiko,Shirai Mitsuyuki [他]
日本獣醫學会会誌 73(7), 953-956, 2011-07
NAID 40018935667

溶質移動シミュレーションを用いた二重濾過膜血漿交換(DFPP)の安全な施行

鈴木尚紀,蓮池由起子,徳山正徳 [他]
日本透析医学会雑誌 44(6), 543-550, 2011-06
NAID 40018912659

Related Pictures

★リンクテーブル★

リンク元	「血液凝固因子」「接着分子」「フィブリノゲン」「インテグリン」
拡張検索	「fibrinogen deficiency」「abnormal fibrinogen」「human fibrinogen」「dysfibrinogenemia」

「血液凝固因子」

fibrinogen gamma chain
Identifiers
Symbol	FGG
Entrez	2266
HUGO	3694
OMIM	134850
RefSeq	NM_021870
UniProt	P02679
Other data
Locus	Chr. 4 q28

fibrinogen beta chain
Identifiers
Symbol	FGB
Entrez	2244
HUGO	3662
OMIM	134830
RefSeq	NM_005141
UniProt	P02675
Other data
Locus	Chr. 4 q28

fibrinogen alpha chain
	Crystallographic structure of a fragment of human fibrin.
Identifiers
Symbol	FGA
Entrez	2243
HUGO	3661
OMIM	134820
RefSeq	NM_000508
UniProt	P02671
Other data
Locus	Chr. 4 q28

　　[★]

英: coagulation factor (Z), clotting factor, blood coagulation factor, blood coagulation factors
関: ビタミンK

血液凝固因子

表

PT.261

型	名称	同義語	分子量 (kDa)	血漿中濃度 (μg/ml)	半減期 (day)
内因系のプロ酵素	XII	Hageman因子	80	29	2
	プレカリクレイン	Fletcher因子	88	45
	XI	PTA	160	4	2.5
ビタミンK依存	VII	proconvertin	50	0.5	0.2
凝固プロ酵素	IX	Christmas因子	57	4	1
	X	Stuart因子	57	8	1.5
	II	プロトロンビン	70	150	3
補助因子	III	組織因子		0
	血小板ホスホリピド
	高分子量キニノゲン		120	70
	V	proaccelerin	330	7	1.5
	VIII	抗血友病因子			0.5
フィブリン堆積因子	I	フィブリノゲン	340	2500	4.5
	XIII	フィブリン安定因子	320	8	7
抑制物質	アンチトロンビンIII		58	150	2.5

標準血液病学 p.217

15種類ある

凝固因子	慣用語・同義語	ビタミンK依存	血液中半減期(hr)	産生器官	染色体座乗部位
I	fibrinogen		100-150	肝臓	4q26
II	prothronbin	○	50-80	肝臓	11p141-q12
III	tissue thromboplastin			体の各組織	1pter-p21
IV	calcium ion			肝臓
V	labile factor/proaccelerin		24	肝臓	1q21-q25
VII	stable factor/proconvertin	○	6	肝臓	13q34
VIII	antihemophilic factor		12	細網系?	xq28
IX	Christmas factor	○	24	肝臓	xq26.3-q27.2
X	Stuart factor	○	25-60	肝臓	13q34
XI	plasma thromboplastin antecedent		40-80	肝臓	4q35
XII	Hageman factor		50-70	肝臓	5q33-qter
XIII	fibrin stabilizing factor		150	肝臓	6p24-p21.3
prekallikrein	Fletcher factor		35	肝臓	4q35
hight molecular weight kininogen	Fitzgerold factor		150	肝臓	3q26-qter
von Willebrand factor			24	血管内皮血小板糸球体	12pter-p12

産生部位

ほとんどが肝臓
例外：

第III因子(F III)：組織トロンボプラスチン：組織
第VIII因子(F VIII)：組織トロンボプラスチン：細網組織？

臨床関連

ビタミンK欠乏
妊娠により第XI因子、第XIII因子を除き、血液凝固因子の濃度が上昇する

-凝固因子

「接着分子」

　　[★]

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

「フィブリノゲン」

　　[★]

英: fibrinogen, Fbg Fib
同: 凝固第I因子第I因子 factor I、フィブリノーゲン、線維素原
商: フィブリノゲンHT
関: フィブリン、血液凝固因子、血液凝固

トロンビンより分解を受け、フィブリンモノマーを生じる。
肝臓で産生さて、血漿中に存在
340kDa
血中半減期：3-4日

機能

一次止血の際に、フィブリノゲンは血小板のGpIIb/IIIaを介して架橋し、一次止血にも貢献する。
凝固因子(第I因子)として血液凝固に関与。具体的にはトロンビンによりフィブリンに変換され、第XIII因子によりフィブリン網を形成して二次止血に資する。
血管外のフィブリンは感染の拡大を防御するらしい

分解されるまでの過程

フィブリンやフィブリノゲンはプラスミンにより分解されフィブリン/フィブリノゲン分解産物(FDP)となり、網内系で処理される。

フィブリノゲンの量に影響を与える要素

減少

産生の低下
出血に対する止血による消費
プラスミンによる分解な

増加

(急性相反応性物質)炎症(感染症など)、悪性腫瘍
妊娠

フィブリノゲンの解釈

低値

先天性疾患(先天性の低フィブリノゲン血症、フィブリノゲン異常症、無フィブリノゲン血症)
後天性疾患(重症肝臓疾患：産生低下、播種性血管内凝固(DIC)：消費亢進)

高値

妊娠？

「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