title: [NKG2D-mediated natural killer cell cytotoxicity against myeloid leukemia cells OUN-1].
abstract: OBJECTIVE
  To investigate NK cell cytotoxicity to leukemic cell by NKG2D receptors and NKG2D ligands interaction upregulated by hydroxyurea (HU).
  
  
  METHODS
  Leukemic cell lines OUN-1 and primary leukemic cells were cultured for 24 hours in the presence of HU, then the NKG2D ligands expressions were analyzed by flow cytometry (FCM). Isolated NK cells from healthy individual cultured for 72 hours in presence of IL-2 were used as effect cell, and leukemic cell line OUN-1 treated with HU was used as target cell, NK cell cytotoxicity against leukemic cell line was assessed using chromium-51 release assay.
  
  
  RESULTS
  Leukemic cell lines showed upregulation of MIC A/B (MFI: 8.9 ± 0.9 vs 23.5 ± 3.4, P = 0.01) and ULBP2 (MFI: 14.5 ± 0.6 vs 33.5 ± 4.8, P = 0.03) following incubation with HU. HU also upregulated the NKG2DLs on primary leukemia cells from patients with acute myeloid leukemia. Treatment of OUN-1 with HU significantly increased the cytotoxicity of NK cells isolated from healthy individual \[(62.0 ± 5.6)% vs (76.0 ± 5.3)%, P = 0.02\], and the enhancing effect of HU was partly blocked by anti-NKG2D Abs \[(76.0 ± 5.3)% vs (46.0 ± 4.5)%, P = 0.00\].
  
  
  CONCLUSIONS
  HU selectively upregulated NKG2D ligand expression on leukemic cell lines, and enhanced NK cell cytotoxicity against leukemic cells through NKG2D receptors and NKG2D ligands interaction.
authors.affiliation: Department of hematology, the Affiliated Hospital of Southeast University, Zhongda Hospital, Jiangsu 210009, China.
authors.forename: Xu-zhang
authors.initials: XZ
authors.lastname: Lu
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Cai
authors.forename: Ling-di
authors.initials: LD
authors.lastname: Ma
authors.forename: Bao-an
authors.initials: BA
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D007938:Leukemia / Q000276:immunology; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology*
chemical_list: D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D006918:Hydroxyurea