C1-inhibitor and the alternative complement pathway – never too late

Abstract

C1-inhibitor belongs to the family of serine protease inhibitors, and controls the activation of several of the plasma cascade systems, including the factor XII contact activation and the kallikrein–kinin systems. The classical complement pathway is controlled by C1-inhibitor regulating both the autoactivation of C1 and the inactivation of C1r and C1s after their activation by external agents, such as immune complexes and C-reactive protein. The mannose-binding lectin (MBL) pathway resembles the classical pathway, MBL replacing C1q and several MBL-associated serine proteases (MASPs) replacing C1r and C1s. Thus, it is not surprising that C1-inhibitor is also an important regulator of the MASPs. The third initial activation mechanism – the alternative complement pathway – has been known for many decades and characterized in detail. It comprises factors B, D and C3, serves as a positive-feedback loop amplified by properdin, and is kept under strict control by the soluble regulatory factors I and H, and several membrane-complement regulators.