Coagulation factor XII, Human, mAb 10-11-37

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Monoclonal antibody 10-11-37 recognizes Coagulation Factor XII (FXII, Hageman factor). FXII is aserine protease and plays a role in blood coagulation, fibrinolysis, kinin and complement systems. Theprotein is the zymogen of the serine protease factor XIIa (FXIIa). FXII is converted to FXIIa throughautoactivation induced by contact to charged surfaces, also known as the plasma contact system. FXIIis predominantly synthesised in the liver and is composed of fibronectin type I and II domains, twoepidermal growth factor-like domains, a kringle region, a proline-rich domain and a catalytic domain. Itsmolecular weight is approximately 80kDa on SDS-PAGE gel electroforeses. The protein circulates inthe plasma at a concentration of 30-35 µg/ml.FXII forms the plasma contact system together with high molecular weight kininogen and plasmakalikrein. FXII autoactivates when these three proteins form a complex on negatively chargednonphysiological surfaces, like inorganic surfaces (eg silicon tubes) or macromolecular organic surfaces(eg heparin) bound to the surface of different cell types, including endothelial cells, platelets andneutrophils. It can trigger blood coagulation and generation of proinflammatory bradykinin. After surfacecomplexation, FXII autoactivates into FXIIa, also called factor XII fragment(XIIf). Once small amountsof kalikrein are formed a positive feedback loop is active leading to enhanced conversion into FXIIa.The activation leads to a series of active enzyme formation. FXIIa converts prekallikrein to kallikrein andkallikrein digests kinogen to liberate proinflammatory bradykinin. Bradykinin triggers inflammatoryreactions via activating endothelial cells resulting in vasodilatation, increased vascular permeability andproduction of other mediators like nitric oxide.The contact system has the ability to activate the complement system via the classical pathway.Simultaneous activation of both systems may lead to pathological conditions, like hereditaryangioedema in individuals with dysfunctional C1-inhibitor (C1-IHB). FXIIa can activate complementprotein C1r and to a lesser degree C1s in absence of C1-IHB. This leads to unimpeded bradykininformation resulting in angioedema. Other interactions with complement system are found on the levelof gC1qR and MASP-1. The antibody is specific for the heavy chain of FXIIa.