Treatment of human immunodeficiency virus-infected lymphocytes with cationized human immunoglobulins.
Hyperimmune immunoglobulins from human immunodeficiency virus (HIV)-infected persons may inhibit intracellular viral replication if the HIV immunoglobulins (HIVIG) are delivered to intracellular spaces where the virus replicates. This study examines the hypothesis that cationized forms of HIVIG undergo enhanced absorptive-mediated endocytosis into cells and inhibit HIV replication. HIVIG and nonimmune human intravenous immunoglobulin (IVIG) were cationized with hexamethylenediamine to an isoelectric point (pI) > 9.5. Cationization markedly increased the binding and endocytosis of HIVIG and IVIG by human peripheral blood lymphocytes (PBL). Cationized HIVIG and IVIG (250 micrograms/mL) resulted in a 90% inhibition in p24 released to the medium in HIV-1-infected human PBL. The study demonstrates that cationization of human immunoglobulin preparations, such as HIVIG and IVIG, markedly increases the endocytosis of immunoglobulin and the inhibition of HIV-1 replication in human PBL.
Pardridge
W M
WM
Department of Medicine, University of California, School of Medicine, Los Angeles 90024.
Buciak
J
J
Yang
J
J
Diagne
A
A
D002412:Cations; D004247:DNA / Q000096:biosynthesis; D003959:Diamines; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007525:Isoelectric Focusing; D007700:Kinetics; D008214:Lymphocytes / Q000276:immunology / Q000382:microbiology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014779:Virus Replication / Q000187:drug effects*
D002412:Cations; D003959:Diamines; D016756:Immunoglobulins, Intravenous; D007457:Iodine Radioisotopes; D014316:Tritium; D004247:DNA; D013936:Thymidine; C007297:1,6-diaminohexane