D-Mannose as a component of the macrophage surface receptor for macrophage-activating factor (MAF) in mice

Abstract

Mouse peritoneal exudate macrophages were rendered cytostatic and cytolytic for various mouse tumor cells in vitro by exposure to partially purified lymphokines containing macrophage-activating factor (MAF) at 37 °C for 2 hr. The macrophage activation disappeared completely when either 0.1 M d-mannose or 0.1 M methyl- d-mannoside was present with MAF. On the other hand, neither d-galactose nor d-glucose inhibited the activation, and l-fucose, l-rhamnose, and N-acetyl- d-glucosamine inhibited it only partially. Incubation of either macrophages or MAF with 0.1 M d-mannose for 2 hr had no effect on activation of the macrophages by the MAF. Treatment of the macrophages by α- d-mannosidase rendered them no longer responsive to MAF. Macrophages treated by either neuraminidase or proteolytic enzymes, but not with β- d-galactosidase lost their ability to respond to MAF. Treatment of MAF with α- d-mannosidase did not affect MAF activity. In addition, MAF activity was not reduced by passage through a column of immobilized concanavalin A. In an absorption experiment, the presence of d-mannose was shown to prevent the adsorption of MAF to macrophages, while d-galactose did not. Treatment of macrophages with plant lectins having affinity for d-mannose, sialic acid or l-fucose prevented the adsorption of MAF, but the other lectins did not. Mouse MAF failed to adsorb to guinea pig peritoneal exudate macrophage, which were suggested as having a fucose-containing glycolipid as a lymphokine receptor. Taken together, these results strongly suggest that the receptor for MAF on mouse macrophages may be a glycoprotein containing d-mannose and sialic acid as essential components.