Contact activation system

The two arms of the contact system. PKa's cleavage of HK liberates BK and promotes inflammation. FXIIa's cleavage of FXI initiates coagulation.

In the contact activation system or CAS, three proteins in the blood, factor XII (FXII), prekallikrein (PK) and high molecular weight kininogen (HK), bind to a surface and cause blood coagulation and inflammation. FXII and PK are proteases and HK is a non-enzymatic co-factor. The CAS can activate the kinin–kallikrein system and blood coagulation through its ability to activate multiple downstream proteins. The CAS is initiated when FXII binds to a surface and reciprocal activation of FXII and PK occurs, forming FXIIa and PKa. FXIIa can initiate the coagulation cascade by cleaving and activating factor XI (FXI), which leads to formation of a blood clot. Additionally, the CAS can activate the kinin–kallikrein system when PKa cleaves HK to form cHK, releasing a peptide known as bradykinin (BK). BK and its derivatives bind to bradykinin receptors B1 and B2 to mediate inflammation.[1][2][3]

Surfaces and activation

Artificial negatively charged substances that activate FXII include L-homocysteine, heparan sulfates, chondroitin sulfates, dermatan sulfate, uric acid crystals, lipoproteins, ferritin and porphyrins. However, the physiological substances or surfaces that activate FXII are still under debate. These may include proteins, such as gC1q-R, aggregated proteins, amyloid, collagen, nucleic acids, and polyphosphates.[4][5][6] The ability of FXII to bind to negatively charged surfaces and activate coagulation forms the basis of the aPTT test, in which artificial materials act as a surface for contact activation. This test is used to measure the contact activation pathway (intrinsic pathway) and the common pathway of clotting.[7] FXII is a zymogen, which means that it requires processing to attain its catalytic protease activity. Upon binding to surfaces, FXII alters in its conformation, giving it low-level protease activity. This change in conformation also promotes its cleavage by PKa and cleavage by FXIIa itself. FXIIa can cleave PK producing PKa, producing a positive feed-back to activate both enzymes. HK binds to PK and is required to locate PK at the surface for activation by FXII.[8]

Zinc has been reportedly demonstrated to be crucial in inducing a conformational change in both FXII and HK as it is required for assembly of FXII and HK bound PK on some negatively charged surfaces. Zinc is suggested to mediate binding of FXII and HK to negatively charged surfaces including gC1q-R and Polyphosphates.[9][10][11]

Contact factors binding to bacteria and viruses

Although contact factors FXII and HK bound PK have been reported to interact with endothelial cells (via gC1q-R), platelets (via Polyphosphate) and Leukocytes; bacteria (Streptococcus pyogenes, Salmonella, and Escherichia coli) and viruses (Hantavirus and Herpes simplex 1 virus) have also been demonstrated to bind to contact factors.[12] Negatively charged lipopolysaccharide (LPS) or surface associated negatively charged teichoic acids from S. aureus[13] and long chain Polyphosphate have all been shown to induce contact activation and bradykinin release thereby contributing to the host-defense reactions[14] by activating the complement cascade.[15]

Physiological roles

Although the contact system can activate FXI and the subsequent clotting cascade, and it is routinely observed to activate coagulation in the presence of medical devices,[16] the actual role of the contact system in normal physiological coagulation remains contentious. This is primarily due to the fact that deficiencies in the contact system proteins FXII, PK and HK do not produce bleeding disorders.[17]

The contact activation system's physiological role in the kinin-kallikrein system is more clear. Here, after activation of PK to PKa by FXIIa, PKa cleaves HK. This produces cleaved HK (cHK), releasing a small peptide known as bradykinin. This peptide binds to bradykinin receptor B2 and its derivative, Des-Arg9-bradykinin binds to bradykinin receptor B1. Upon ligand binding, these receptors mediate inflammatory responses.[18]

Roles in disease

Activation of the CAS is associated with hereditary angioedema, a disorder characterised by episodes of swelling.[19] Genetic knockout studies in murine models of cardiovascular disease and genetic linkage studies in humans have implicated the contact factors in contributing to diverse cardiovascular disease processes including thrombosis[20][21][22] and stroke.[23]

References

  1. ^ Schmaier, AH (May 2014). "Physiologic activities of the contact activation system". Thrombosis Research. 133 Suppl 1 (1): S41–4. doi:10.1016/j.thromres.2014.03.018. PMC 4004333. PMID 24759141.
  2. ^ de Maat, S; Tersteeg, C; Herczenik, E; Maas, C (June 2014). "Tracking down contact activation - from coagulation in vitro to inflammation in vivo". International Journal of Laboratory Hematology. 36 (3): 374–81. doi:10.1111/ijlh.12222. PMID 24750684.
  3. ^ Monika Pathak, Bubacarr Gibril Kaira, Alexandre Slater and Jonas Emsley (2018). "Cell Receptor and Cofactor Interactions of the Contact Activation System and Factor XI". Frontiers in Medicine. 5: 66. doi:10.3389/fmed.2018.00066. PMC 5871670. PMID 29619369.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Ghebrehiwet, B; Kaplan, AP; Joseph, K; Peerschke, EI (November 2016). "The complement and contact activation systems: partnership in pathogenesis beyond angioedema". Immunological Reviews. 274 (1): 281–289. doi:10.1111/imr.12469. PMID 27782339. S2CID 2787614.
  5. ^ Naudin, C; Burillo, E; Blankenberg, S; Butler, L; Renné, T (November 2017). "Factor XII Contact Activation". Seminars in Thrombosis and Hemostasis. 43 (8): 814–826. doi:10.1055/s-0036-1598003. PMID 28346966. S2CID 22844127.
  6. ^ Schmaier, AH (January 2016). "The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities". Journal of Thrombosis and Haemostasis. 14 (1): 28–39. doi:10.1111/jth.13194. PMID 26565070.
  7. ^ Naudin, C; Burillo, E; Blankenberg, S; Butler, L; Renné, T (November 2017). "Factor XII Contact Activation". Seminars in Thrombosis and Hemostasis. 43 (8): 814–826. doi:10.1055/s-0036-1598003. PMID 28346966. S2CID 22844127.
  8. ^ de Maat, S; Tersteeg, C; Herczenik, E; Maas, C (June 2014). "Tracking down contact activation - from coagulation in vitro to inflammation in vivo". International Journal of Laboratory Hematology. 36 (3): 374–81. doi:10.1111/ijlh.12222. PMID 24750684.
  9. ^ Røjkjær R, Schousboe I (1997). "Partial Identification of the Zn2+-Binding Sites in Factor XII and its Activation Derivatives". European Journal of Biochemistry. 247 (2): 491–496. doi:10.1111/j.1432-1033.1997.00491.x. PMID 9266689.
  10. ^ Schousboe I (1993). "Contact activation in human plasma is triggered by zinc ion modulation of factor XII (Hageman factor)". Blood Coagul Fibrinolysis. 4 (5): 671–8. doi:10.1097/00001721-199310000-00002. PMID 7507361.
  11. ^ Rasmus KBJKJER and Inger SCHOUSBOE (1997). "The surface-dependent autoactivation mechanism of factor XII". Eur. J. Biochem. 243 (1–2): 160–166. doi:10.1111/j.1432-1033.1997.0160a.x. PMID 9030735.
  12. ^ Mattsson E, Herwald H, Cramer H, Persson K, Sjöbring U, Björck L (2001). "Staphylococcus aureus Induces Release of Bradykinin in Human Plasma". Infection and Immunity. 69 (6): 3877–3882. doi:10.1128/IAI.69.6.3877-3882.2001. PMC 98413. PMID 11349054.
  13. ^ Kalter ES, van Dijk WC, Timmerman A, Verhoef J, Bouma BN (1983). "Activation of purified human plasma prekallikrein triggered by cell wall fractions of Escherichia coli and Staphylococcus aureus". The Journal of Infectious Diseases. 148 (4): 682–691. doi:10.1093/infdis/148.4.682. PMID 6355312.
  14. ^ Morrissey JH, Choi SH, and Smith SA (2012). "Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation". Blood. 119 (25): 5972–5979. doi:10.1182/blood-2012-03-306605. PMC 3383012. PMID 22517894.
  15. ^ Nickel, KF; Renné, T (2012). "Crosstalk of the plasma contact system with bacteria". Thrombosis Research. 130: S78 – S83. doi:10.1016/j.thromres.2012.08.284. PMID 23026673.
  16. ^ Jaffer, IH; Fredenburgh, JC; Hirsh, J; Weitz, JI (June 2015). "Medical device-induced thrombosis: what causes it and how can we prevent it?". Journal of Thrombosis and Haemostasis. 13 (Suppl 1): S72–81. doi:10.1111/jth.12961. PMID 26149053.
  17. ^ de Maat, S; Tersteeg, C; Herczenik, E; Maas, C (June 2014). "Tracking down contact activation - from coagulation in vitro to inflammation in vivo". International Journal of Laboratory Hematology. 36 (3): 374–81. doi:10.1111/ijlh.12222. PMID 24750684.
  18. ^ Schmaier, AH (January 2016). "The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities". Journal of Thrombosis and Haemostasis. 14 (1): 28–39. doi:10.1111/jth.13194. PMID 26565070.
  19. ^ De Maat, S; Hofman, ZLM; Maas, C (19 June 2018). "Hereditary angioedema: the plasma contact system out of control". Journal of Thrombosis and Haemostasis. 16 (9): 1674–1685. doi:10.1111/jth.14209. PMID 29920929.
  20. ^ Fredenburgh JC, Gross PL, and Weitz JI (2017). "Emerging anticoagulant strategies" (PDF). Blood. 129 (2): 147–154. doi:10.1182/blood-2016-09-692996. PMID 27780803.
  21. ^ Pierre-Emmanuel Morange; et al. (2011). "KNG1 Ile581Thr and susceptibility to venous thrombosis" (PDF). Blood. 117 (13): 3692–3694. doi:10.1182/blood-2010-11-319053. PMID 21270443. S2CID 39069970.
  22. ^ Revenko AS; et al. (2011). "Selective depletion of plasma prekallikrein or coagulation factor XII inhibits thrombosis in mice without increased risk of bleeding". Blood. 118 (19): 5302–5311. doi:10.1182/blood-2011-05-355248. PMC 4425441. PMID 21821705.
  23. ^ Yi Wu (2015). "Contact pathway of coagulation and inflammation". Thrombosis Journal. 13: 17. doi:10.1186/s12959-015-0048-y. PMC 4421925. PMID 25949215.

Read other articles:

Ann Sophie

Ann Sophie Ann Sophie lors de l'émission Unser Song für ÖsterreichInformations générales Surnom Ann Sophie Nom de naissance Ann Sophie Dürmeyer Naissance 1er septembre 1990 (33 ans)Londres, Angleterre Activité principale Chanteuse, Auteur-Compositeur Genre musical Pop Années actives Depuis 2011 modifier Ann Sophie Dürmeyer, dite Ann Sophie, née le 1er septembre 1990 à Londres, est une chanteuse allemande. Elle est née en Angleterre de parents allemands qui sont peu après re...

 

Kyustendil

Sudut kota Kyustendil Kyustendil (Bulgaria: Кюстендил) merupakan sebuah kota di Bulgaria. Kota ini letaknya di bagian barat. Tepatnya di Provinsi Kyustendil, dekat perbatasan Republik Makedonia. Pada tahun 2007, kota ini memiliki jumlah penduduk sebesar 51.872 jiwa. Kota ini terletak pada ketinggian 513 m. Gallery Kota kembar Cocoa Beach, Florida, Amerika Serikat Pranala luar KnCity.info, a website about Kyustendil Kyustendil at Journey.bg Kyustendil at BGGlobe Regional History Museu...

 

Haundorf

Haundorf. Haundorf adalah kota yang terletak di distrik Weißenburg-Gunzenhausen di Bavaria, Jerman. Kota Haundorf memiliki luas sebesar 51.34 km² . Haundorf pada tahun 2006, memiliki penduduk sebanyak 2.668 jiwa. lbsKota dan kotamadya di Weissenburg-GunzenhausenAbsberg | Alesheim | Bergen | Burgsalach | Dittenheim | Ellingen | Ettenstatt | Gnotzheim | Gunzenhausen | Haundorf | Heidenheim | Höttingen | Langenaltheim | Mar...

German submarine U-43 (1939)

German world war II submarine For other ships with the same name, see German submarine U-43. U-37, (an identical U-boat to U-43) at Lorient in 1940 History Nazi Germany NameU-43 Ordered21 November 1936[1] BuilderAG Weser, Bremen[1] Yard number948[1] Laid down15 August 1938[1] Launched23 May 1939[1] Commissioned26 August 1939[1] FateSunk south-west of the Azores by an American aircraft, 30 July 1943. 55 dead[1] General characteristics Cla...

 

2023 Under-20 Intercontinental Cup

Football match Football match2023 Under-20 Intercontinental CupLa Bombonera, venue of the match Boca Juniors AZ 1 1 Boca Juniors won 4–1 on penaltiesDate9 September 2023VenueLa Bombonera, Buenos AiresRefereeGery Vargas (Bolivia)Attendance37,386WeatherSunny18 °C (64 °F)← 2022 2024 → The 2023 Under-20 Intercontinental Cup (Spanish: Sub-20 Intercontinental 2023) was the second edition of the UEFA–CONMEBOL Under-20 Intercontinental Cup, a one-off football match organis...

 

Kfarfakoud

This date+December 2010 needs additional citations for verification. Please help improve this article by adding citations to reliable sources in this date+December 2010. Unsourced material may be challenged and removed.Find sources: Kfarfakoud – news · newspapers · books · scholar · JSTOR (December 2010) (Learn how and when to remove this template message) Kfarfakoud (Kfarfakud or Kafarfakoud كفرفاقود) is a village in the Chouf district of ...

Belk

American retail chain For other uses, see Belk (disambiguation) and Bełk (disambiguation). Belk, Inc.FormerlyNew York Racket (1888–1898)Belk Brothers (1898–1909)Company typePrivateIndustryRetailFounded1888 (136 years ago) (1888) in Monroe, North Carolina, United StatesFounderWilliam Henry BelkHeadquartersCharlotte, North Carolina, United StatesNumber of locations293 (2019)[1]Key peopleDon Hendricks (CEO)ProductsClothing, footwear, bedding, furniture, jewelry, beauty...

 

Kelowna International Airport

International airport in British Columbia, Canada Kelowna International AirportIATA: YLWICAO: CYLWWMO: 71203SummaryAirport typePublicOwnerTransport Canada[1]OperatorCity of KelownaServesKelowna, British ColumbiaTime zonePST (UTC−08:00) • Summer (DST)PDT (UTC−07:00)Elevation AMSL1,420 ft / 433 mCoordinates49°57′26″N 119°22′41″W / 49.95722°N 119.37806°W / 49.95722; -119.37806Websiteylw.kelowna.caMapCYLWLocation in Britis...

 

Persian Gulf Residency

Colonial subdivision of the British-Indian Empire Persian Gulf Residencyالمقيمية السياسية البريطانية في الخليج الفارسی1822–1971 Flag of the East India CompanyStatusResidency of the East India Company(1822–1858) Residency of the British Indian Empire (1858-1947)Group of British protectorates(1947–1971)CapitalBushehr (1822–1946)Manama (1946–1971)Official languagesEnglishCommon languagesArabic, PersianReligion IslamStates under Persian...

Hymenogastraceae

Family of fungi Hymenogastraceae Hymenogaster sublilacinus Scientific classification Domain: Eukaryota Kingdom: Fungi Division: Basidiomycota Class: Agaricomycetes Order: Agaricales Family: HymenogastraceaeVittad. (1831) Type genus HymenogasterVittad. (1831) Genera see text The Hymenogastraceae is a family of fungi in the order Agaricales with both agaric and false-truffle shaped fruitbodies.[1] Formerly, prior to molecular analyses, the family was restricted to the false-truffle gene...

 

Filippo Balbi

Pour les articles homonymes, voir Balbi. Filippo BalbiNaissance 1806NaplesDécès 27 septembre 1890AlatriPériode d'activité 1855Nationalité italienne (17 mars 1861 - 27 septembre 1890)Activité PeintreFormation Académie des beaux-arts de Naplesmodifier - modifier le code - modifier Wikidata Filippo Balbi, né en 1806 à Naples, et mort le 27 septembre 1890 à Alatri, est un peintre italien, actif dans un style archaïque représentant des scènes allégoriques et religieuses. Biographie ...

 

Ираклеониты

Ираклеониты — ученики гностика Ираклеона (II век). Упоминаются как особая секта Епифанием и Августином; при крещении и миропомазании они соблюдали обряд помазания елеем и при этом произносили воззвания на арамейском языке, которые должны были освободить душу от власт�...

Jon McLaughlin (footballer)

Scottish footballer For similarly named people, see John McLaughlin. Jon McLaughlin McLaughlin with Scotland in 2019Personal informationFull name Jonathan Peter McLaughlin[1]Date of birth (1987-09-09) 9 September 1987 (age 36)[1]Place of birth Edinburgh, ScotlandHeight 6 ft 3 in (1.91 m)[1]Position(s) GoalkeeperTeam informationCurrent team RangersNumber 33Senior career*Years Team Apps (Gls)2006–2007 Harrogate Railway Athletic 21 (0)2007–2008 Har...

 

土库曼斯坦总统

土库曼斯坦总统土库曼斯坦国徽土库曼斯坦总统旗現任谢尔达尔·别尔德穆哈梅多夫自2022年3月19日官邸阿什哈巴德总统府（Oguzkhan Presidential Palace）機關所在地阿什哈巴德任命者直接选举任期7年，可连选连任首任萨帕尔穆拉特·尼亚佐夫设立1991年10月27日 土库曼斯坦土库曼斯坦政府与政治 国家政府 土库曼斯坦宪法 国旗 国徽 国歌 立法機關（英语：National Council of Turkmenistan） ...

 

علاقات الجبل الأسود الخارجية

في استفتاء أجري في 21 أيار / مايو 2006 ، اختار شعب الجبل الأسود مغادرة اتحاد دولة صربيا والجبل الأسود . تم تأكيد هذه النتيجة بإعلان برلمان الجبل الأسود الاستقلال في 3 يونيو 2006. في نفس الوقت طلبت الجبل الأسود من المجتمع الدولي الاعتراف بها كما أوضحت أهداف سياستها الخارجية. كما ور�...

Grotta Gigante

Giant cave on the Italian side of the Trieste Karst Grotta Gigante (Giant Cave)Briška jama, Briškovska jama, Jama pri BriščikihInside the cave looking towards the tourist entranceLocation of the caves in ItalyLocationSgonico (TS, Friuli-Venezia Giulia, Italy)Coordinates45°42′33.18″N 13°45′49.79″E / 45.7092167°N 13.7638306°E / 45.7092167; 13.7638306Depth115 m (377 ft)Length280 m (920 ft)Elevation275 m[1]Discovery1840GeologyKar...

 

Ion Nicolaescu

Moldovan footballer (born 1998) Ion Nicolaescu Nicolaescu with Heerenveen in 2023Personal informationDate of birth (1998-09-07) 7 September 1998 (age 25)Place of birth Chișinău, MoldovaHeight 1.84 m (6 ft 0 in)Position(s) ForwardTeam informationCurrent team HeerenveenNumber 18Youth career2008–2014 Cahul-20052014–2016 Zimbru ChișinăuSenior career*Years Team Apps (Gls)2016–2017 Zimbru-2 Chișinău 37 (13)2016–2018 Zimbru Chișinău 25 (5)2018–2020 Shakhtyor Sol...

 

هرموبوليس

هرموبوليس (إرموبولي) Ερμούπολη Ermoupoli   الموقع الجغرافي تقسيم إداري البلد اليونان[1] عاصمة لـ جنوب إيجة  المنطقة الإدارية جنوب إيجة الكيكلادس خصائص جغرافية إحداثيات 37°26′22″N 24°56′17″E / 37.4395°N 24.9381°E / 37.4395; 24.9381   المساحة 11.2 كيلومتر مربع  الأرض 11.3 كم² ا...

John Heartfield

Pour les articles homonymes, voir Heartfield. John HeartfieldAu IVe congrès de l'Association des artistes visuels de la RDA (1959, Leipzig).Naissance 19 juin 1891Berlin-Schmargendorf, Empire allemandDécès 26 avril 1968 (à 76 ans)Berlin-Est, Allemagne de l'EstSépulture Cimetière de DorotheenstadtPériode d'activité 1910-1968Nom de naissance Helmut HerzfeldAutres noms John Tom Harry HeartfieldNationalité allemandeActivité Photographe artiste peintreFormation libraire, arts appliq...

 

0 (عام)

  لمعانٍ أخرى، طالع 0 (توضيح). 0معلومات عامةجزء من عقد 0 الاستعمال ترقيم السنة الفلكية بتاريخ 1 ق.م المواليد (en) 2 ق م 1 م تعديل - تعديل مصدري - تعديل ويكي بيانات ► | قرن -1 | << قرن 0 >> | قرن 1 | ◄ ► | عقد -20 | عقد -10 | عقد 0 | << عقد 10 >> | عقد 20 | عقد 30 | عقد 40 | ◄ ► | ► | -4 | -3 | -2 | -1 | &l...