Fig. 1. Activation pathways of the complement system. The complement system is activated by the classical, lectin, or alternative pathways. The initiation of the classical pathway involves the C1 protein complex, which consists of C1q, C1r, and C1s. Upon activation, C1s cleaves C4 and C2. In the lectin pathway, activation occurs when mannose-binding lectin (MBL) encounters a pathogenic carbohydrate motif. Subsequently, MBL associates with MASP-1 and MASP-2, leading to the cleavage of C4 and C2. The resulting cleavage products induce the formation of C3 convertase C4bC2a, which subsequently splits C3 into C3a and C3b. C3a has the ability to induce the chemotaxis and activation of microglia via C3aR. Additionally, C3b can undergo cleavage to form iC3b, which is recognized by microglial cells through complement receptor 3 (CR3), thereby promoting activation. Furthermore, the production of C3b can facilitate the generation of C5 convertase (C4bC2aC3b, C3bBbC3b). C5 can also be cleaved into C5a and C5b, with C5a further promoting the chemotaxis and activation of glial cells through C5aR. Another pathway involves the spontaneous hydrolysis of C3 to C3 (H2O). All three pathways result in the generation of convertases, which subsequently stimulate the production of the primary components of the complement system, namely anaphylatoxins (C4a, C3a, and C5a), membrane attack complexes, and opsonins (C3b). Allergic toxins initiate pro-inflammatory signaling, while C5b associates with C6, C7, C8, and C9 to form membrane attack complexes (MAC), ultimately resulting in cell cleavage.
© Korean J Pain
