The structure and function of vertebrate mannose lectin-like proteins

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Abstract
Sugar-specific recognition is now well established as an important determinant of cell–cell interactions and host defence mechanisms. Macrophages, in particular, are known to express a variety of lectin-like proteins that are specific for oligosaccharides terminating in mannose, fucose, galactose and sialic acid. This review focuses on mannose recognition systems. Terminal mannose is rarely found on mammalian cell surfaces whereas it is ubiquitous on the surfaces of lower organisms. Mammals have evolved at least two mechanisms to recognize terminal mannose residues. These are, first, a mannose receptor located on the surface of macrophages and second, a mannose-binding protein found in blood plasma and secreted by hepatocytes. The mannose receptor is a 175K (K = 103 M r) membrane glycoprotein. The receptor binds glycoproteins bearing high-mannose chains avidly at neutral pH but poorly at pH 5–6. The receptor recycles rapidly between the cell surface, where ligand binding occurs, and various acid intracellular compartments, where the ligand is discharged. The pH dependency of binding and the rapid recycling of receptor allow cells to accumulate many ligand molecules over an extended time. Endocytosis via this pathway appears to be regulated since mannose receptor expression is closely regulated. For example, the receptor is absent from monocytes but strongly expressed on 3- to 4-day-old monocyte-derived macrophages. Receptor expression can be up- and down-regulated by anti-inflammatory steroids and γ interferon, respectively. The mechanisms are poorly understood as is the physiological basis for modulation. The mannose-binding protein is a large oligomeric plasma protein secreted by liver and present in significant amounts in serum. The basic subunit of the mannose-binding protein is a 32K protein, which shows homology with other lectin-like proteins, notably certain surfactant proteins of the lung. The structure of the mannose-binding protein has been deduced from sequence information and DNA cloning experiments. The elaboration of the mannose-binding protein by the liver is regulated; it appears to be an acute phase reactant. Recent evidence suggests that the mannose-binding protein may play some opsonic role in the recognition and killing of organisms. In this review, it is suggested that the mannose receptor and the mannose-binding protein operate ‘hand in glove’ to deal with infectious agents that express mannose on their surfaces.

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