Roles of Serum Lectins in Host Defense

Abstract

Mannan-binding protein (MBP), also called mannose-binding protein (MBP) or mannanbinding lectin (MBL), is a Ca2+-dependent (C-type) mammalian lectin specific for mannose, N-acetylglucosamine (GlcNAc), and fucose, and is an important serum component associated with innate immunity. Human MBP is a homooligomer of an approximately 31 kDa subunit, each subunit containing a carbohydrate recognition domain (CRD) followed by a short neck region on the COOH terminal side and a collagen-like domain followed by a short cysteine-rich region on the NH2 terminal side. Three subunits form a structural unit, and MBP normally consists of 3–6 structural units joined through disulfide bonds at the NH2 termini, the whole molecular mass being approximately 300–600 kDa. MBP is a pattern-recognition molecule of the innate immune system that promotes phagocytosis of microorganisms through “the lectin pathway” of complement activation when it binds to ligand sugars such as mannose and GlcNAc on microbes (Kawasaki 1999) (see Fig. 1). More recently, MBP was found to have potent growth inhibitory activity to human colorectal carcinoma cell line, SW1116, in vivo via a complement- independent mechanism (Ma et al. 1999). This was proposed to term MBP-dependent cell-mediated cytotoxicity (MDCC). The MBP-ligand oligosaccharides expressed on the surface of SW1116 cells, which were assumed to be associated with MDCC, were isolated and characterized (Terada et al. 2005). Endogenous ligands for MBP were shown to be expressed highly in the brush border epithelial cells of kidney proximal tubules, and both meprin α and β have been identified as novel endogen MBP ligand proteins.