Effects of X-RAY Irradiation on Natural Killer (NK) Cell System. II. Increased Sensitivity to Natural Killer Cytotoxic Factor (NKCF)

1989 ◽  
Vol 11 (2-3) ◽  
pp. 521-534 ◽  
Author(s):  
A. Uchida ◽  
Y. Mizutani ◽  
M. Nagamuta ◽  
M. Ikenaga
1985 ◽  
Vol 162 (5) ◽  
pp. 1512-1530 ◽  
Author(s):  
G Degliantoni ◽  
M Murphy ◽  
M Kobayashi ◽  
M K Francis ◽  
B Perussia ◽  
...  

We characterize the natural killer (NK) cell colony-inhibiting activity (CIA) produced in supernatants from cultures of human peripheral blood lymphocytes (PBL) with NK-sensitive target cell lines, and study its relationship with NK cell-derived cytotoxic factor (NKCF). Using monoclonal antibodies (mAb) specific for NK cells or other lymphocyte populations, we unambiguously identify NK cells as the only PBL subset able to produce both NKCF and NK-CIA. We present functional and biochemical data suggesting that NKCF and NK-CIA represent the same molecule: (a) a highly significant positive correlation exists between the quantity of NKCF and NK-CIA in supernatants independently produced by different PBL subsets; (b) both NK-CIA and NKCF are induced by culture of PBL with NK-sensitive, but not with NK-insensitive cell lines, and with HLA-DR+ bone marrow cells; (c) both NKCF and NK-CIA are absorbed on the same cell lines or bone marrow cell types; (d) the two activities coelute in the same gel filtration fractions; (e) D-mannose-6-phosphate blocks both NKCF and NK-CIA activity, and prevents their absorption by K562 cells; and (f) both NKCF and NK-CIA activity are lost after 2 d at 37 degrees C. The NK-CIA-containing preparations are devoid of antiviral activity, and antiinterferon (anti-IFN) antibodies do not block the inhibitor activity of NK-CIA. The effect of NK-CIA on day 14 (early) colony-forming units of granulocytes and macrophages (CFU-GM) is synergistic with that of IFN-gamma, and this synergy is also evident on day 7 (late) CFU-GM growth. A combination of NK-CIA and IFN-gamma suppresses late CFU-GM, at concentrations of the two lymphokines that are completely ineffective when used independently. No synergy between NK-CIA and IFN-alpha or -beta was observed, due to a direct inhibitory effect of these two IFN types on late CFU-GM. Antibodies specific for tumor necrosis factor (TNF), but not those specific for lymphotoxins, inhibit both NK-CIA and NKCF activity in the NK cell-derived supernatant. Recombinant TNF, in the range of concentrations corresponding to that of the cytotoxic activity on L-929 cells present in supernatants, mediated both NKCF and NK-CIA activity.(ABSTRACT TRUNCATED AT 400 WORDS)


Blood ◽  
2005 ◽  
Vol 105 (9) ◽  
pp. 3615-3622 ◽  
Author(s):  
Pegah Nowbakht ◽  
Mihai-Constantin S. Ionescu ◽  
Andreas Rohner ◽  
Christian P. Kalberer ◽  
Emmanuel Rossy ◽  
...  

AbstractNatural killer (NK) cell–mediated cytolytic activity against tumors requires the engagement of activating NK receptors by the tumor-associated ligands. Here, we have studied the role of NKG2D and natural cytotoxicity receptors (NCRs) in the recognition of human leukemia. To detect as-yet-unknown cell-surface molecules recognized by NCRs, we developed soluble forms of NKp30, NKp44, and NKp46 as staining reagents binding the putative cognate ligands. Analysis of UL16-binding protein-1 (ULBP1), ULBP2, and ULBP3 ligands for NKG2D and of potential ligands for NKp30, NKp44, and NKp46 in healthy hematopoietic cells demonstrated the ligand-negative phenotype of bone marrow–derived CD34+ progenitor cells and the acquisition of cell-surface ligands during the course of myeloid differentiation. In acute myeloid leukemia (AML), leukemic blasts from approximately 80% of patients expressed very low levels of ULBPs and NCR-specific ligands. Treatment with differentiation-promoting myeloid growth factors, together with interferon-γ, upregulated cell-surface levels of ULBP1 and putative NCR ligands on AML blasts, conferring an increased sensitivity to NK cell–mediated lysis. We conclude that the ligand-negative/low phenotype in AML is a consequence of cell maturation arrest on malignant transformation and that defective expression of ligands for the activating NKG2D and NCR receptors may compromise leukemia recognition by NK cells.


1997 ◽  
Vol 55 (4) ◽  
pp. 273-282 ◽  
Author(s):  
Youko Nakada ◽  
Yuka Tsukatani ◽  
Toshifumi Kosaka ◽  
Masato Kuwabara ◽  
Shigeo Tanaka ◽  
...  

1980 ◽  
Vol 151 (3) ◽  
pp. 614-627 ◽  
Author(s):  
B Blazar ◽  
M Patarroyo ◽  
E Klein ◽  
G Klein

Superinfection of latently Epstein-Barr virus (EBV)-carrying Raji cells with the P3HR-1 substrain EBV, known to induce the entry of a substantial fraction of cells into an abortively lytic cycle, increased the susceptibility of the cells to natural killer (NK) effect of human blood lymphocytes. Reciprocal cold-target competition tests with known NK-cell sensitive and -resistant lymphoid cell ines showed that the increased susceptibility is a result of the appearance of an NK-sensitive target, rather than to a general increase in membrane fragility. Lymphocytes of EBV-seropositive and -negative donors were equally effective killers against P3HR-1 virus-superinfected targets. EBV-induced NK sensitivity increased with time. It was a result of some event associated with the intracellular viral cycle, and not to the adherence of viral particles to the cell surface. Induction of EBV-carrying P3HR-1 cells to entry into the viral cycle with n-butyrate also increased their NK sensitivity. A transforming, noncytopathic prototype strain of EBV, B95-8, failed to increase the susceptibility of theRaji cells to NK-lysis, although it had some effect on the Daudi line. Because NK cells can kill virus-producing cells at an early stage of the cycle, before the virus particles are assembled, they may restrict, in vivo, the spread of the virus from latently infected cells.


2020 ◽  
Author(s):  
Guanjun Deng ◽  
Xinghua Peng ◽  
Zhihong Sun ◽  
Wei Zheng ◽  
Jia Yu ◽  
...  

Nature has always inspired robotic designs and concepts. It is conceivable that biomimic nanorobots will soon play a prominent role in medicine. In this paper, we developed a natural killer cell-mimic AIE nanoterminator (NK@AIEdots) by coating natural kill cell membrane on the AIE-active polymeric endoskeleton, PBPTV, a highly bright NIR-II AIE-active conjugated polymer. Owning to the AIE and soft-matter characteristics of PBPTV, as-prepared nanoterminator maintained the superior NIR-II brightness (quantum yield ~8%) and good biocompatibility. Besides, they could serve as tight junctions (TJs) modulator to trigger an intracellular signaling cascade, causing TJs disruption and actin cytoskeleton reorganization to form intercellular “green channel” to help themselves crossing Blood-Brain Barriers (BBB) silently. Furthermore, they could initiatively accumulate to glioblastoma cells in the complex brain matrix for high-contrast and through-skull tumor imaging. The tumor growth was also greatly inhibited by these nanoterminator under the NIR light illumination. As far as we known, The QY of PBPTV is the highest among the existing NIR-II luminescent conjugated polymers. Besides, the NK-cell biomimetic nanorobots will open new avenue for BBB-crossing delivery.


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