Understanding the Role of C1 Inhibitor in Inflammation Control
We’ve often explored the coagulation cascade on our blog, but one important aspect that deserves more attention is its connection to inflammation, particularly through Factor XII (FXII).
The Dual Role of Factor XII
Factor XII (FXII) is a critical protein that sits at the intersection of blood clotting and inflammation. When overactivated, it can trigger thrombo-inflammation, a powerful and sometimes harmful combination of coagulation and immune response.
Under normal circumstances, this system is kept in balance by C1 Inhibitor (C1-INH), one of the body’s natural “brakes.” However, when C1-INH is deficient, due to hereditary or acquired mutations, the regulatory control falters. The result is excessive activation of FXIIa and kallikrein, leading to increased inflammation, vascular damage, and conditions such as angioedema, stroke, or even neurodegeneration.
How the Contact Activation Pathway Works
The contact activation pathway links clotting and inflammation in a tightly regulated sequence. It begins when inactive FXII encounters charged or damaged surfaces, such as misfolded proteins or cell debris. This contact converts FXII into its active form, FXIIa, which then transforms prekallikrein into kallikrein.
Kallikrein further amplifies the process by activating additional FXII molecules, creating a positive feedback loop. Along with high-molecular-weight kininogen (HK), these proteins form the contact system. As kallikrein cleaves HK, it releases bradykinin, a potent molecule that widens blood vessels, increases permeability, and attracts immune cells to the site of injury.
FXIIa also engages the intrinsic coagulation pathway, promoting thrombin generation and fibrin clot formation. While this is not essential for routine bleeding control, excessive activity can exacerbate disease-related clotting and inflammation.
C1 Inhibitor: The Essential Brake
To maintain balance, C1 Inhibitor (C1-INH) regulates FXIIa and kallikrein activity. When C1-INH levels fall, bradykinin accumulates unchecked, causing the hallmark swelling and inflammation of hereditary angioedema (HAE). Fortunately, several recently approved therapies target FXIIa or the kallikrein-bradykinin pathway, helping restore control and reduce vascular leakage in HAE patients.
Quick Facts: FXII-Related Inflammation
- FXIIa connects clotting and inflammation.
- Overactivation triggers thrombo-inflammation, combining clotting and immune signaling.
- Unchecked activity can damage blood vessels and brain tissue, contributing to stroke, neurodegeneration, and angioedema.
Explore Related Research Tools
Innovative Research offers a range of human and mouse Factor XII, C1-Inhibitor, Prekallikrein, and Kininogen products, available as ELISA kits, purified proteins, and recombinant forms.
Have questions? Contact our team at sales@innov-research.com, we’re happy to help.
Citations
Schematic overview of Factor XII-mediated pathways in edema and... | Download Scientific Diagram
FDA Approves Garadacimab-gxii in Hereditary Angioedema | AJMC
FDA Approves Garadacimab-gxii in Hereditary Angioedema
Author(s)Pearl Steinzor
