From the Research
No, C1 inhibitor does not cleave the C3b-Bb complex. C1 inhibitor primarily regulates the classical and lectin pathways of complement activation by inhibiting C1r, C1s, and MASPs (mannose-associated serine proteases), but it does not directly interact with or cleave the C3b-Bb complex, which is the C3 convertase of the alternative pathway.
Key Points
- The C3b-Bb complex is instead regulated by other complement regulatory proteins such as Factor H, Factor I, decay-accelerating factor (DAF/CD55), and membrane cofactor protein (MCP/CD46) 1.
- These regulators either promote the dissociation of the complex (decay acceleration) or serve as cofactors for the proteolytic inactivation of C3b by Factor I.
- C1 inhibitor's main function is to prevent excessive activation of the complement system at the initial stages of the classical and lectin pathways, as well as regulating the contact, fibrinolytic, and kinin systems, but it does not have enzymatic activity to cleave the C3b-Bb complex.
- According to the most recent study, C1 inhibitor has multiple functions including non-covalent interactions with other proteins, cell surfaces, or lipids, but cleaving the C3b-Bb complex is not one of them 2.
Mechanism of Action
- C1 inhibitor binds to a variety of extracellular matrix components, including type IV collagen, laminin, entactin, and fibrinogen, which may serve to concentrate C1 inhibitor at extravascular inflammatory sites 3.
- C1 inhibitor also interacts with E and P selectins on endothelial cells, resulting in suppression of leukocyte rolling and transmigration 3.
- Additionally, C1 inhibitor binds directly to Gram-negative bacteria, leading to suppression of the development of sepsis 3.