title: NF-kappaB signaling, elastase localization, and phagocytosis differ in HIV-1 permissive and nonpermissive U937 clones.
abstract: To identify positive or negative factors for HIV-1 infectivity, clones from the U937 promonocytic cell line that express similar levels of CD4 and CXCR4, but differ in HIV-1 susceptibility, were compared. In contrast to HIV-1 permissive clone 10 (plus), nonpermissive clone 17 (minus) was adherent to coverslips coated with chemokines, was phagocytic, killed bacteria, and expressed human leukocyte elastase (HLE) in a granule-like compartment (HLEG) that was never detected at the cell surface (HLECS). In contrast to the minus clone, the plus clone expressed HLE on the cell surface and was adherent to coverslips coated with the HLECS ligands alpha1proteinase inhibitor (alpha1PI, alpha1antitrypsin) and the HIV-1 fusion peptide. The phosphorylation status of several important signaling proteins was studied at the single cell level. Tumor suppressor p53, NF-kappaB p65, and Akt were constitutively phosphorylated in the plus clone, but not in the minus clone. Surprisingly, both alpha1PI and LPS induced phosphorylation of NF-kappaB p65 Ser-536 in both clones, but induced dephosphorylation of Ser-529 in the plus clone only. HIV-1 permissivity was conferred to the minus clone in a manner that required stimulation by both alpha1PI and LPS and was coincident to NF-kappaB p65 phosphorylation/dephosphorylation events as well as translocation of HLE to the cell surface. Even when stimulated, the minus clone exhibited greater reverse transcriptase activity, but less p24, than the plus clone. Results presented suggest that HIV-1 uptake and production efficiency are influenced by signaling profiles, receptor distribution, and the phagocytic capacity specific to the stage of differentiation of the CD4+ target cell.
authors: Institute for Human Genetics and Biochemistry, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10003, USA. Cynthia.Bristow@mssm.edu
authors: Cynthia L
authors: CL
authors: Bristow
authors: Roland
authors: R
authors: Wolkowicz
authors: Maylis
authors: M
authors: Trucy
authors: Aaron
authors: A
authors: Franklin
authors: Fernando
authors: F
authors: Di Meo
authors: Mark T
authors: MT
authors: Kozlowski
authors: Ronald
authors: R
authors: Winston
authors: Roland R
authors: RR
authors: Arnold
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D018925:Chemokines / Q000037:antagonists & inhibitors; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019272:Leukocyte Elastase / Q000032:analysis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000032:analysis / Q000378:metabolism; D010587:Phagocytosis; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018925:Chemokines; D000939:Epitopes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D015842:Serine Proteinase Inhibitors; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D012694:Serine; D051057:Proto-Oncogene Proteins c-akt; D012697:Serine Endopeptidases; D019272:Leukocyte Elastase