The human mannose-binding protein (MBP) is a multimeric serum protein that is divided into three domains: a cysteine-rich NH2-terminal domain that stabilizes the alpha-helix of the second collagen-like domain, and a third COOH-terminal carbohydrate binding region. The function of MBP is unknown, although a role in host defense is suggested by its ability to bind yeast mannans. In this report we show that native and recombinant human MBP can serve in an opsonic role in serum and thereby enhance clearance of mannose rich pathogens by phagocytes. MBP binds to wild-type virulent Salmonella montevideo that express a mannose-rich O-polysaccharide. Interaction of MBP with these organisms results in attachment, uptake, and killing of the opsonized bacteria by phagocytes. These results demonstrate that MBP plays a role in first line host defense against certain pathogenic organisms.
Mammalian mannose-binding proteins (MBP)' were first isolated from the serum of rabbits (1), and subsequently were found in the liver and serum ofhumans (2-5) and rodents (5-8). Analysis of the encoded human MBP, like its two rat homologues (9), reveals that the protein is divided into three domains: a cysteine-rich NH2-terminal domain which stabilizes the a helix of the second collagen-like domain, and a third COOH-terminal carbohydrate-binding region (10). MBP may have a role in host defense; this is suggested first by its ability to bind high mannose glycans, which are present in the cell walls of many pathogens, including some Gramnegative bacteria (11-13), mycobacteria (14), yeasts and fungi, certain parasites (15), and envelope glycoproteins of certain viruses, such as the human immunodeficiency virus (HIV) (16,17). Second, the synthesis of human MBP appears to be stress induced, as it is an acute-phase protein (10). Third, human MBP is a member of a family of homologous lectin-like proteins (18) that includes proteins found in the coelomic fluid of sea urchins (19) and in the hemolymph of Sacraphaga perigintaa (20), which may have a role in the host defense of these organisms.We wish to evaluate whether the high mannose oligosaccharides identified on the HIV envelope glycoprotein (gp120) were potential ligands for MBP. gp120, isolated from HIVinfected CD4+ H9 lymphoblasts (18) and recombinant gp120 expressed in Chinese Hamster Ovary (CHO) cells (Gregory, T., and M. Spellman, a personal communication) has been shown to possess high mannose glycans. The importance of these high-mannose oligosaccharides in HIV target interaction is suggested by studies showing that plant lectins that recognize certain configurations ofhigh-mannose oligosaccharides inhibit HIV infection and syncytia formation in vitro (21) . These conclusions are supported by studies that show that deglycosylated forms of gp120 (22) as well as bacterially expressed recombinant gp120 bind with reduced affinity
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