Gangliosides of monocyte-derived macrophages of adults with advanced HIV infection show reduced surface accessibility

Abstract: Gangliosides of macrophages are potent immunoregulatory molecules. A monoclonal anti-body directed at human macrophage gangliosides (25F4) inhibits macrophage migration with relative specificity. Recent reports suggested that greater expression of GM1 in mononuclear cells accompa-nies advanced HIV infection, although others failed to demonstrate any differences in vitro. We puri-fied gangliosides from blood monocyte-derived mac-rophages obtained from HIV-infected adults. Densi-tometric analysis of chromatograms demonstrated no differences in relative quantities of any macro-phage gangliosides among all HIV-positive and-negative donors. Antibody 25F4 showed equiva-lent ELISA reactivity with purified macrophage gangliosides of HIV-positive and-negative donors. However, intact macrophages of HIV donors with CD41 cell counts F200/mm3 showed impaired im-munofluorescent surface expression of the 25F4 epitope and concomitant loss of migration inhibi-tory responsiveness. Thus, although relative con-tent is unchanged, macrophage gangliosides be-come surface-inaccessible in adults with advanced HIV infection. Our data provide further evidence that dysregulation of glycosphingolipid metabolism in HIV-1 infection contributes to immune dysfunc