Natural Killer Cytotoxic Factor (Nkcf) as Mediator in the Lytic Pathway of Nk Cell Mediated Cytotoxicity*

2018 ◽  
pp. 91-104
Author(s):  
Benjamin Bonavida ◽  
Susan C. Wright
Keyword(s):  
Natural Killer ◽  
Nk Cell ◽  
Cytotoxic Factor

scholarly journals Natural killer (NK) cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor. Relationship with tumor necrosis factor and synergism with immune interferon.

1985 ◽  
Vol 162 (5) ◽  
pp. 1512-1530 ◽  
Author(s):  
G Degliantoni ◽  
M Murphy ◽  
M Kobayashi ◽  
M K Francis ◽  
B Perussia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Necrosis Factor ◽  
Natural Killer ◽  
Cell Lines ◽  
Tumor Necrosis ◽  
Nk Cell ◽  
Inhibiting Activity ◽  
Ifn Gamma ◽  
Cytotoxic Factor ◽  
Necrosis Factor

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)

Relationship between radical production and natural killer cytotoxic factor (NKCF) in canine natural killer (NK) cell-mediated cytotoxicity

1997 ◽  
Vol 55 (4) ◽  
pp. 273-282 ◽  
Author(s):  
Youko Nakada ◽  
Yuka Tsukatani ◽  
Toshifumi Kosaka ◽  
Masato Kuwabara ◽  
Shigeo Tanaka ◽  
...  
Keyword(s):  
Natural Killer ◽  
Nk Cell ◽  
Cytotoxic Factor ◽  
Radical Production

Natural Killer Cell Inspired AIE Nanoterminator for Blood-Brain-Barrier Crossing via Tight-Junction Modulation and NIR-II Gliomas Theranostics

2020 ◽  
Author(s):  
Guanjun Deng ◽  
Xinghua Peng ◽  
Zhihong Sun ◽  
Wei Zheng ◽  
Jia Yu ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Natural Killer ◽  
Intracellular Signaling ◽  
Soft Matter ◽  
Tumor Imaging ◽  
Nk Cell ◽  
Killer Cell ◽  
Light Illumination ◽  
Blood Brain ◽  
Intracellular Signaling Cascade

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.

scholarly journals Normalized natural killer (NK) cell activity in long-term remission of acute leukaemia

1983 ◽  
Vol 55 (2) ◽  
pp. 305-309 ◽  
Author(s):  
Yasuhiro Yoda ◽  
Tsukasa Abe ◽  
Akio Tashiro ◽  
Shinsaku Hirosawa ◽  
Kenichi Kawada ◽  
...  
Keyword(s):  
Natural Killer ◽  
Acute Leukaemia ◽  
Nk Cell ◽  
Cell Activity ◽  
Nk Cell Activity

scholarly journals Natural Killer Cells Are Present in Rag1−/− Mice and Promote Tissue Damage During the Acute Phase of Ischemic Stroke

2021 ◽  
Author(s):  
Leoni Rolfes ◽  
Tobias Ruck ◽  
Christina David ◽  
Stine Mencl ◽  
Stefanie Bock ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Adoptive Transfer ◽  
Immune Cell ◽  
Nk Cell ◽  
Cell Subset ◽  
Neurological Deficits ◽  
In Vitro Assays ◽  
Experimental Stroke ◽  
Transfer Model

AbstractRag1−/− mice, lacking functional B and T cells, have been extensively used as an adoptive transfer model to evaluate neuroinflammation in stroke research. However, it remains unknown whether natural killer (NK) cell development and functions are altered in Rag1−/− mice as well. This connection has been rarely discussed in previous studies but might have important implications for data interpretation. In contrast, the NOD-Rag1nullIL2rgnull (NRG) mouse model is devoid of NK cells and might therefore eliminate this potential shortcoming. Here, we compare immune-cell frequencies as well as phenotype and effector functions of NK cells in Rag1−/− and wildtype (WT) mice using flow cytometry and functional in vitro assays. Further, we investigate the effect of Rag1−/− NK cells in the transient middle cerebral artery occlusion (tMCAO) model using antibody-mediated depletion of NK cells and adoptive transfer to NRG mice in vivo. NK cells in Rag1−/− were comparable in number and function to those in WT mice. Rag1−/− mice treated with an anti-NK1.1 antibody developed significantly smaller infarctions and improved behavioral scores. Correspondingly, NRG mice supplemented with NK cells were more susceptible to tMCAO, developing infarctions and neurological deficits similar to Rag1−/− controls. Our results indicate that NK cells from Rag1−/− mice are fully functional and should therefore be considered in the interpretation of immune-cell transfer models in experimental stroke. Fortunately, we identified the NRG mice, as a potentially better-suited transfer model to characterize individual cell subset-mediated neuroinflammation in stroke.

scholarly journals The m15 Locus of Murine Cytomegalovirus Modulates Natural Killer Cell Responses to Promote Dissemination to the Salivary Glands and Viral Shedding

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 866
Author(s):  
Baca Chan ◽  
Maja Arapović ◽  
Laura Masters ◽  
Francois Rwandamuiye ◽  
Stipan Jonjić ◽  
...  
Keyword(s):  
Nk Cells ◽  
Salivary Glands ◽  
Natural Killer ◽  
Nk Cell ◽  
Acute Infection ◽  
Killer Cell ◽  
Viral Escape ◽  
Murine Cytomegalovirus ◽  
Viral Shedding ◽  
Cell Responses

As the largest herpesviruses, the 230 kb genomes of cytomegaloviruses (CMVs) have increased our understanding of host immunity and viral escape mechanisms, although many of the annotated genes remain as yet uncharacterised. Here we identify the m15 locus of murine CMV (MCMV) as a viral modulator of natural killer (NK) cell immunity. We show that, rather than discrete transcripts from the m14, m15 and m16 genes as annotated, there are five 3′-coterminal transcripts expressed over this region, all utilising a consensus polyA tail at the end of the m16 gene. Functional inactivation of any one of these genes had no measurable impact on viral replication. However, disruption of all five transcripts led to significantly attenuated dissemination to, and replication in, the salivary glands of multiple strains of mice, but normal growth during acute infection. Disruption of the m15 locus was associated with heightened NK cell responses, including enhanced proliferation and IFNγ production. Depletion of NK cells, but not T cells, rescued salivary gland replication and viral shedding. These data demonstrate the identification of multiple transcripts expressed by a single locus which modulate, perhaps in a concerted fashion, the function of anti-viral NK cells.

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