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The Requirements of Mannose Binding Lectin (MBL) Pathway

The mannose-binding lectin (MBL) pathway activates complement cascade through


mannose-binding lectin protein to evade innate immunity. The pathway need some basic
components to activate the complement system. The basic components of mannose-binding
lectin (MBL) pathway include mannose-binding lectin (MBL), MASPs, complexes, enzymes and
formation of membrane attack complex.
Mannose Binding Lectin (MBL) can activate complement cascade by binding to
carbohydrates moieties (N-acetyl-glucosamine, mannose, fucose or glucose) present on the
surface of pathogens (Gal & Ambrus, 2001). It has similarities with structure of C1q and can
activates complement cascade without the presence of antibody and C1 complex (Hamvas et al.,
2005).
MBL is a family of proteins called collectins. It consists of collagenous domains and lectin
domains (Eddie, Takahashi, Ezodyekwitz & Stuart, 2009). Cluster of genes found on the long
arm of chromosome 10 in humans encodes for collectins (Eddie et al., 2009).
The MBL is a serum protein synthesized from the liver (Takahashi & Ezekowitz, 2005). MBL
can recognize wide range of microorganisms such as gram-positive and gram-negative bacteria,
yeasts, parasites, mycobacteria and virus (Takahashi & Ezekowitz, 2005). Human serum MBL
protein has similar structure with C1q, however identical polypeptide chains (32kDa) join to
form the molecule. Trimerization of these polypeptide into subunits form a larger oligomers
(Wallis, 2007). There are some differences in different species although the composition of MBL
oligomers are generally the same. For example, human MBL made up of dimers to hexamers of
the subunits (Gal & Ambrus, 2001). It circulates as oligomers of trimers with the highest-order of
oligomer as a hexamer of trimers (Takahashi & Ezekowitz, 2005).
MBL
MASPs (MBL-associated serine proteases) are proteins that are associated with MBL
protein. MASPs are homologous of C1r and C1s of the classical pathway (Wallis, 2007). They
have C1r/C1s/Uegf /bone morphogenic protein 1 and many others which are highly conserved
domain structures (Takahashi et al., 2008). There are four types of MASPs, which are MASP-1,
MASP-2, MASP-3 and MAp19 (Ip, Takahashi, Ezekowitz & Stuart, 2009). MASP-1 and MASP-

2 are encoded by distinct genes and have serine protease domain (Ip et al, 2009). The MASP-3
and MAp19 are alternatively spliced products MASP-1 and MASP-2 respectively (Ip et al,
2009). Schwaeble (as cited in Youssif et al., 2012) found MAp19 lack of serine protease domain
and it regulates lectin pathway by competing for binding of MASPs to the carbohydrate
molecule. The MASPs normally circulate as zymogens in complexes with MBL (Sorensen &
Thiel, 2005).
The other basic components of complexes. The complexes involve in the activation of
mannose-binding lectin pathway includes C4, C2, C3 and C5. These complexes are important as
when they are cleaved into fragments, the bigger fragments will bind to the surface of pathogens
and initiate the formation of membrane attack complex (MAC) that leads to lysis of the cell. On
the other hand, the smaller fragments of cleaved complexes such as C3a, C4a and C5a known as
anaphylatoxins. Anaphylatoxins are fragments that are produced after the activation of
complement system. The anaphylatoxins act on mast cells to release histamine and promotes
inflammation.
Lastly is the membrane attack complex (MAC). Membrane attack complex made up of
C5b6789 which anchor on the surface of pathogens cell membrane and make a channel that
causes the internal cell moves out of the cell called cell lysis.