The complement system is a potent component of the innate immune response, promoting inflammation and orchestrating defense against pathogens. Complement activation is initiated by the pattern-recognition molecules complement component C1q, mannose-binding lectin (MBL) and ficolins (H-ficolin, L-ficolin, M-ficolin), which typically recognize antibody-antigen complexes or foreign polysaccharides. The associated proteases (C1r, C1s, MASP-1 and MASP-2) then activate the complement system. The serpin C1-inhibitor (C1-inh) blocks activity of all these complexes and has been successfully used in models of disease. Many structures of these components became available recently, including that of C1-inh, facilitating the structure-guided design of drugs targeting complement activation. Complement-mediated inflammation has been linked to ischemia-reperfusion injury, organ graft rejection and even neurodegeneration, so targeting this process has direct clinical implications.
1. Beinrohr L, et al. (2008). C1, MBL–MASPs and C1-inhibitor: novel approaches for targeting complement-mediated inflammation. Trends in molecular medicine, 14(12), 511-521.
2. Laudisi F, et al. (2013). Cutting edge: the NLRP3 inflammasome links complement-mediated inflammation and IL-1β release. The Journal of Immunology, 191(3), 1006-1010.