Lectin pathway

Natta projection of mannose in its α-D-mannopyranose form. Mannan is a polymer of mannose.

The lectin pathway is a type of cascade reaction in the complement system, similar in structure to the classical complement pathway,^[1] in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade. In contrast to the classical complement pathway, the lectin pathway does not recognize an antibody bound to its target. The lectin pathway starts with mannose-binding lectin (MBL) or ficolin binding to certain sugars.

In this pathway, mannose-binding lectin binds to mannose, glucose, or other sugars with 3- and 4-OH groups placed in the equatorial plane, in terminal positions on carbohydrate or glycoprotein components of microorganisms including bacteria such as Salmonella, Listeria, and Neisseria strains. Fungal pathogens such as Candida albicans and Cryptococcus neoformans as well as some viruses such as HIV-1 and Respiratory syncytial virus (RSV) are bound by MBL.

Mannan-binding lectin, also called mannose-binding protein, is a protein belonging to the collectin family that is produced by the liver and can initiate the complement cascade by binding to pathogen surfaces.

MBL

MBL forms oligomers of subunits, which are trimers (6- to 18-heades correspond to a dimer and a hexamer, respectively). Multimers of MBL form a complex with MASP1 (Mannose-binding lectin-Associated Serine Protease), MASP2 and MASP3, that are protease zymogens. The MASPs are very similar to C1r and C1s molecules of the classical complement pathway, respectively, and are thought to have a common evolutionary ancestor. When the carbohydrate-recognising heads of MBL bind to specifically arranged mannose residues on the surface of a pathogen, MASP-1 and MASP-2 are activated to cleave complement components C4 and C2 into C4a, C4b, C2a, and C2b. In addition, two smaller MBL-associated proteins (MAps) are found in complex with MBL. MBL-associated protein of 19 kDa (MAp19) and MBL-associated protein of 44 kDa (Map44). MASP-1, MASP-3 and MAp44 are alternative splice products of the MASP1 gene, while MASP-2 and MAp19 are alternative splice products of the MASP-2 gene. MAp44 has been suggested to act as a competitive inhibitor of lectin pathway activation, by displacing MASP-2 from MBL, hence preventing cleavage of C4 and C2 ^[2]

C3 convertase

C4b and C2a combine on the surface of the pathogen to form C3-convertase (C4b and C2a), while C4a and C2b act as chemoattractants. C3 convertase is, in classical terms, C4b2a.

Clinical significance

It has been found that people deficient in MBL experience a substantial increase in infections during the early years of childhood. [citation needed]

See also

• Classical complement pathway
• Alternative complement pathway
• Mannan-binding lectin

References

External links

• http://pathmicro.med.sc.edu/ghaffar/complement.htm