Background of the Lectin Pathway
The innate immune system is the host's first line of defense against infection and consists of humoral and cellular immunity that can recognize potential pathogens within minutes or hours of entry. The complement system is a mainstay of innate immunity and plays an important role in the immediate response against microorganisms. The complement system can be activated by three pathways, namely the classical pathway, the alternative pathway and the evolutionary more ancient lectin pathway.
The lectin pathway consists of soluble pattern recognition molecules (PRM) containing collagen-like regions, such as mannan lectin (MBL), L-ficolin (ficolin-2), and H-ficolin (ficolin-3), etc. Both MBL and ficolins depend on MBL-associated serine proteases (MASP) to activate the complement system. On binding of MBL-MASP or ficolin- MASP complexes to microbial surfaces, MASP sequentially cleaves C4 and C2, thereby generating the C3 convertase C4bC2b, which results in opsonization and lysis of pathogens and recruitment of inflammatory cells and eliminates microorganisms.
How is Complement Activated in Lectin Pathway?
Similar to classical pathway activation, lectin pathway activation occurs through pattern recognition. The lectin pathway is initiated when PRM bind to oligosaccharides and acetylated residues on the surface of microorganisms, respectively. There are five different PRMs that can activate the complement system via the lectin pathway, including MBL, ficolins (ficolin-1, ficolin-2, ficolin-3), and CL-LK. After binding to the target molecule, MBL, CL-KL, and ficolins form complexes with MBL-associated serine proteases 1 and 2 (MASP-1 and MASP-2), resulting in activation of the MASPs and subsequent cleavage of C4 into C4a and C4b.
C4b is bound to the membrane, while C4a is released into the microenvironment. Activated MASPs can also cleave C2 into C2a and C2b. C2a binds to the membrane and C2b is released into the microenvironment. Functionally, C4b and C2b combine to form the C3 convertase (C4b2a), which cleaves C3 into C3a and C3b. C3b binds to the membrane to form C5 convertase (C4b2a3b), and C3a is released into the microenvironment. The generation of C5 convertase is the end of the lectin pathway.
Fig.1 Lectin pathway activation. (Daha, 2006)
Effector Function of Lectin Pathways Activation
The C5 convertase cleaves C5 into C5a and C5b. C5b sequentially combines with C6, C7, C8, and C9 to generate the membrane attack complex (MAC). Activation of the complement cascade reaction leads to in opsonization, phagocytosis, and lysis of target microorganisms by forming MAC. In addition, complement activation can induce several inflammatory effects, including expression of adhesion molecules, chemotaxis and activation of leukocytes, the release of reactive oxygen species, and secretion of cytokines and chemokines.
Creative Biolabs offers a range of complement test services and complement products related to the lectin pathway, including:
If you are interested in our products or services, please feel free to contact us.
Reference
-
Daha, M. R.; et al. Compliments from complement: a fourth pathway of complement activation? 2006.
Related Product
For Research Use Only.
Related Sections:
