Contact activation system
In the contact activation system or CAS, three proteins in the blood,
Surfaces and activation
Artificial negatively charged substances that activate FXII include L-
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
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]
References
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