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 antibody directed at human macrophage gangliosides (25F4) inhibits macrophage migration with relative specificity. Recent reports suggested that greater expression of G M1 in mononuclear cells accompanies advanced HIV infection, although others failed to demonstrate any differences in vitro. We purified gangliosides from blood monocyte-derived macrophages obtained from HIV-infected adults. Densitometric analysis of chromatograms demonstrated no differences in relative quantities of any macrophage gangliosides among all HIV-positive and -negative donors. Antibody 25F4 showed equivalent ELISA reactivity with purified macrophage gangliosides of HIV-positive and -negative donors. However, intact macrophages of HIV donors with CD 4؉ cell counts F200/mm 3 showed impaired immunofluorescent surface expression of the 25F4 epitope and concomitant loss of migration inhibitory responsiveness. Thus, although relative content is unchanged, macrophage gangliosides become 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 dysfunction. J. Leukoc. Biol. 64: 311-321; 1998.

Impaired Alveolar Macrophage Response to Haemophilus Antigens in Chronic Obstructive Lung Disease

“…After incubation (24 h), nonadherent cells were removed. Remaining alveolar macrophages were consistently 98-100% esterase positive (15,21). Percent viability of alveolar macrophages (mean Ϯ SEM), by trypan blue exclusion, was 77.3 Ϯ 2.5, 82.5 Ϯ 2.9, and 85.1 Ϯ 1.8 for Groups 1, 2, and 3, respectively (p Ͼ 0.1).…”

“…Blood mononuclear cells were purified by density centrifugation and seeded (10 6 cells/well) onto 96-well Linbro tissue culture plates (Hampton Research, Aliso Viejo, CA) as previously detailed (21). After incubation (7-10 d), nonadherent cells were removed.…”

Polyglycosylceramides, Poly-N-acetyllactosamine-Containing Glycosphingolipids: Methods of Analysis, Structure, and Presumable Biological Functions

“…GSLs are also known binders of microbes 3,300 and toxic proteins. , They have been described as receptors for important pathogens such as influenza virus, Helicobacter pylori , , Haemophilus influenzae , Neisseria meningitidis 304 or Escherichia coli . GSLs seem also to be implicated in HIV infections, ,, most probably as immunoregulatory molecules . Regarding toxins, a classical example is the ganglioside GM1 which has been described as a receptor for cholera toxin B-subunit …”

“…305 GSLs seem also to be implicated in HIV infections, 306,307,311 most probably as immunoregulatory molecules. 306 Regarding toxins, a classical example is the ganglioside GM1 which has been described as a receptor for cholera toxin B-subunit. 308 Other examples are ganglioside GD1b which binds to tetanus toxin, 310 paragloboside, nLc 4 Cer, with affinity for heat-labile enterotoxin of Escherichia coli, 309 or ganglioside GT1b which has been suggested to be a component of the receptor complex for Clostridium botulinum type B neurotoxin (BoNT/ B).…”

NontypeableHaemophilus influenzae-binding gangliosides of human respiratory (HEp-2) cells have a requisite lacto/neolacto core structure

“…The importance of macrophage function to NTHI infection is further illustrated by the increased susceptibility to severe, invasive NTHI infections of adults with AIDS [36]. Macrophages of adults with AIDS also have impaired surface expression of gangliosides, including NTHI-binding gangliosides [37]. Thus, identification of a common potential receptor in human macrophages and respiratory epithelial cells provides an important step toward understanding NTHI-glycolipid interactions.…”