The carbohydrate composition of the surface receptor for macrophage migration inhibitory factor (MIF) on guinea pig macrophages has been studied by examining the interaction of MIF with different saccharides and by testing the ability of plant lectins with known saccharide binding affinities to bind to macrophages and block their response to MIF. Comparison of the effectiveness of a variety of natural and synthetic mono- and disaccharides in inhibiting MIF activity in lymphocyte supernatants revealed that inhibitory activity was confined to natural 5-methylpentose sugars (l-fucose > l-rhamnose = 6-deoxy-d-glucose) and synthetic saccharides containing α-fucosyl residues. Observations on the MIF inhibitory activity of synthetic fucosyl glycosides containing fucosyl residues of defined configuration at terminal and subterminal positions indicate that MIF interacts preferentially with terminal α-l-fucopyranosyl residues and does not recognize subterminal saccharides. Studies with disaccharides containing α-(1 → 2)-, α-(1 → 3), and α-(1 → 6)-linked l-fucosyl residues failed to reveal preferential interaction of MIF with any one linkage configuration. Incubation of macrophages before exposure to MIF with lectins that bind to terminal fucosyl residues (Lotus tetragonolobus and Ulex europaeusI, agglutinins) rendered them unresponsive to MIF but lectins which bind to nonterminal fucosyl residues and to other saccharides had no effect. The role of fucosyl residues in the binding of MIF by macrophages is discussed with reference to the possible composition of the MIF receptor and the role of fucose-containing glycolipids as receptors for this lymphokine.
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