Complement, lectin pathway

Lectin pathway, stimulated by binding to a lectin. Lectins belong to a family of proteins called collectins, which are present in blood and bind to bacteria. One lectin, known as the mannose binding lectin (MBL), binds to a sequence of mannose sugars that are part of the carbohydrate on the cell surface of some bacteria. It is the lectin-bacteria complex that activates one of the complement proteins. The components of the pathway are prefixed with a C and a number. 

The reactions that take place in the complement system can be initiated in several ways. During the early phase of infection, lipopoly-saccharides and other structures on the surface of the pathogens trigger the alternative pathway (right). If antibodies against the pathogens become available later, the antigen-antibody complexes formed activate the classic pathway (left). Acute-phase proteins (see p. 276) are also able to start the complement cascade lectin pathway, not shown). 

The classical complement pathway reqnires activation by circulating antibodies, IgM or IgG (specific immnne response), while the alternative and lectin pathways can be activated in the absence of antibody (non-specific immnne response). 

Figure 15.1 Complement activation pathways. The classical, lectin and alternative pathways converge into a final common pathway when C3 convertase (C3 con) cleaves C3 into C3a and C3b. Ab = antibody, Ag = antigen, Cl-INH = Cl inhibitor, MAC = membrane attack complex, MASP = MBL-associated serine protease, MBL = mannose-binding lectin, P = properdin. Overbar indicates activation.

Also see color figure.) Initiation of actron by complement occurs via three pathways classical, alternative (properdin), and lectin pathways. 

Some of the complement activating activity of AAF-IIb2 and IIb-3 still remained even when protein A-Sepharose-passed serum was used for the assay (Fig. 7) [65]. Therefore it is suggested that other mechanisms may also be involved in expression of the complement activating activity of pectic polysaccharides in addition to the classical and alternative pathways. The MBL lectin pathway also has a possibility to be involved in activation of complement by the active pectic polysaccharides (Fig. 1), however, further studies are required. 

Although, as with human disease, complement deposition is not conspicuous in the vasculitic lesions, multiple experimental observations indicate that complement activation has an important pathogenic role in this model (64,65). Depletion of complement with Cobra venom factor completely prevents the development of glomerulonephritis and vasculitis after injection of MPO-IgG or transfer of anti-MPO splenocytes (64). Injection of anti-MPO IgG into mice with knockout of various complement genes demonstrates that the alternative complement pathway, but not the classic pathway or the lectin pathway, is required for anti-MPO IgG mediated disease induction (64). Specifically, C4-/- mice with blockade of the classic pathway and the lectin pathway develop disease that is same as in wild type mice, whereas C5-/-mice with blockade of all pathways and factor B -/- mice with selective blockade of the alternative pathway are completely protected from disease induction. In accord with an important role for complement, the CS-inhibiting monoclonal antibody (BB5.1) prevents the induction of glomerulonephritis in mice after injection of anti-MPO IgG and LPS (65). Even when the anti-C5 antibody is administered a day after the anti-MPO, there is a marked reduction in disease induction. 

Peters C, Kawakami M, Kaul M, Ilg T, Overath P, Aebischer T (1997) Secreted proteophos-phoglycan of Leishmania mexicana amastigotes activates complement by triggering the man-nan binding lectin pathway. Eur J Immunol 27(10) 2666-72. 

T, YANO T (2006), Lectin pathway of bony fish complement identification of two homologs of the mannose-binding lectin associated with MASP2 in the common carp Cyprinus carpio) , J Immunol,m, 5471—9. 

Fujita, T., Evolution of lectin-complement pathway and its role in innate immunity, Nat. Rev. Immunol., 2, 346, 2002. 

Proteins of the Complement System Alternative, Classical, Lectin, and Membrane Attack Pathways and Complement Regulating Proteins... 

Matsushita M, Fujita T. Ficolins and the lectin complement pathway. Immunol Rev 2001 180 78-85-... 

Fujita T, Matsushita M, Endo Y. The lectin-complement pathway—its role in innate immunity and evolution. Immunol Rev 2004 198 185-202. 

Although complement pathways have not been extensively described in bivalves, there are several lines of evidence that support the presence of this defence mechanism in these organisms. The complement system is composed of more than 30 soluble plasma proteins that collaborate to distinguish and eliminate non-self particles. C3 is the central component system. In vertebrates, it is proteolyticaUy activated by a C3 convertase through the classic, lectins and alternative routes (Nonaka and Yoshizaki, 2004). In the classic activation route, immunoglobulins are recognised by the Cl protein, whereas activation is initiated by the recognition of membrane carbohydrates by lectins and ficolins in the lectin route (Nonaka and Kimura, 2006). 

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