Mannose Binding Lectin

Because MBL (also termed mannose-binding protein) has multiple functions, it is the most studied of the collectins. MBL has a "flower bouquet" structure and the circulating serum form is hexameric. Normal serum level in infants is 1780 ng/ml (Turner, 1996).

In the presence of calcium, MBL naturally and selectively binds to sugars such as N-acetylglucosamine, mannose, and N-acetylmannosamine. Binding to sugars is usually weak with a constant of Kd ~ 10-3 M, but the molecule's hexameric nature increases the functional avidity of MBL. MBL is active in host defense, and high concentrations of glucosamine and mannosamine sugars are expressed on bacteria, fungi, HIV, and influenza (Haurum etal., 1993).

MBL can act as an opsonin resulting in the ingestion and killing of MBL coated bacteria. Enhanced phagocytosis may be facilitated by two different receptors for MBL. One receptor is a unique 126-kDa Clq receptor on the surface of macrophages and neutrophils (Tenner et al., 1995). Although the data are controversial, a second collectin receptor has also been described. Composed of two identical 60-kDa chains, this receptor has homology with cal-reticulin, an intracellular calcium-binding protein (Malhotra et al., 1990).

MBL provides a mechanism for activation of the complement system that is independent of antibody. In peripheral blood, MBL circulates in a complex with MBL-associated serine protease (MASP) (Kawakami et al., 1982). In the mouse, this MASP 100-kDa protein has 30-40%homology with Clr and Cls. Moreover, structurally, MASP more closely resembles activated Cls (Matsushita and Fujita, 1992). When the MBL/MASP complex binds to a bacterium, MASP is activated and cleaves both C4 and C2. This results in the creation of a C3 convertase consisting of C4b2a complexes on the bacterial cell wall. Binding of C3b fragments to the cell surface provides multiple opsonins that interact with complement receptors on macrophages and neutrophils. Because the complement pathway is activated solely by lectins, this mechanism has been called the lectin complement activation pathway (Turner, 1996).

There are different forms of both MBL and MASP. In the rat, there are two forms of MBL (types A and C). The oligomeric type A variety has a mass of 650-750 kDa and activates complement. The lower-molecular-mass (200 kDa) type C form does not fix complement. In humans, there may be two forms of MASP. It is not clear whether MASP1 and MASP2 have the same structure and function as the mouse protein (Turner, 1996).

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