Changes in membrane enzymes and glycosphingolipids in lymphocytes from HIV-1--infected and noninfected intravenous drug users.
The amounts of cell-surface glycosphingolipids and plasma membrane enzymes produced on the peripheral blood mononuclear cells (PBMNCs) isolated from 101 intravenous drug users (IDUs), of whom 91 were HIV-1 seropositive, were examined. Seronegative IDUs and age-matched healthy donors served as controls. The numbers of circulating CD3+, CD4+, and CD8+ T lymphocytes decreased during the advanced stages of the infection. There were also fewer CD4+ T-helper cells in HIV-1--seronegative IDU drug addicts. PBMNCs from HIV-1--seropositive subjects had abnormal surface enzyme kinetics. The phospholipase C had two pH optima, whereas the enzyme on normal cells has only one. The specific activity in cells from AIDS subjects was 4 times lower than that in normal PBMNCs. 5'-Nucleotidase showed a similar trend, whereas neutral endopeptidase activity did not correlate with the amounts of surface common acute lymphoblastic leukemia antigen (CALLA). These enzyme activities were decreased in HIV-seronegative IDUs. The subcellular distribution of enzymes and the profile of surface glycosphingolipids were also markedly changed, indicating the profound alterations in the membranes of PBMNCs from HIV-1--seropositive IDUs. These data suggest that intravenous drug use compromises the biochemical and structural integrity of the membrane surface of PBMNCs even before the onset of HIV.
Leoni
L M
LM
Laboratory of Cellular Pathology, Institute of Pathology, Locarno, Switzerland.
Losa
G A
GA
D015720:5'-Nucleotidase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002462:Cell Membrane / Q000201:enzymology; D010450:Endopeptidases / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism*; D005260:Female; D005732:Gangliosides / Q000097:blood; D005982:Glutathione Transferase / Q000378:metabolism; D006028:Glycosphingolipids / Q000097:blood*; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000201:enzymology; D006679:HIV Seropositivity / Q000097:blood / Q000201:enzymology / Q000276:immunology; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D008214:Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid; D015260:Neprilysin / Q000378:metabolism; D012794:Sialic Acids / Q000097:blood; D015819:Substance Abuse, Intravenous / Q000097:blood* / Q000150:complications / Q000201:enzymology; D010738:Type C Phospholipases / Q000378:metabolism
D004798:Enzymes; D005732:Gangliosides; D006028:Glycosphingolipids; D012794:Sialic Acids; D005982:Glutathione Transferase; D015720:5'-Nucleotidase; D010738:Type C Phospholipases; D010450:Endopeptidases; D015260:Neprilysin; D019158:N-Acetylneuraminic Acid