Effects of mannose and mannose derivatives on the clearance of IgG antibody-coated erythrocytes in the rat.

The effects of D-mannose, mannose dimers, mannan, or lactotransferrin [a glycoprotein containing mannose alpha-(1,6) linkages] infusion on the clearance of IgG-coated, 99mTc-labelled, autologous red blood cells (IgG-RBC) by the spleen and liver were investigated in the rat. Untreated autologous rat RBC labelled with 111In were simultaneously injected to correct for 99mTc present in the blood contained in each organ. In normal rats, the mean specific spleen uptake (per g) of IgG-RBC was about 10 times higher than the mean specific liver uptake (per g). Consistent with the clearance curves of IgG-RBC, the mean specific splenic uptake of those RBC significantly decreased after D-mannose, mannose dimers, mannan, or lactotransferrin injections, compared with that measured in normal rats or in control rats receiving i.v. physiological saline, 5% or 15% glucose. In contrast, the mean specific liver uptake of IgG-RBC remained unchanged under otherwise identical experimental conditions. The splenic blockade induced by mannan and mannose derivatives was dose-dependent, C3-independent and spontaneously reversible within 42 hr. Splenic macrophages isolated from mannose- or mannan-treated animals expressed a decreased receptor activity for the Fc domain of IgG, whereas no consistent effect on the C3 receptors was noted. These data show a transient and specific impairment of the Fc(IgG)-receptor function of rat splenic macrophages after the i.v. injection of D-mannose or of mannose derivatives. They support the concept that simple sugar compounds can exhibit immunoregulatory activities in vivo, as has been already shown in vitro.