Dynamic metabolic change of cancer cells induced by natural killer cells at single-cell level studied by label-free mass cytometry

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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MORPHOLOGICAL, PHENOTYPIC AND KARYOTYPIC CHARACTERIZATION OF A NOVEL NATURAL-KILLER-CELL TARGET - EVIDENCE OF INVOLVEMENT OF MHC CLASS-I MOLECULES IN NK CELL RECOGNITION

International Journal of Oncology ◽

10.3892/ijo.5.5.1069 ◽

1994 ◽

Author(s):

G FERLAZZO ◽

R CAVALIERE ◽

ME GAGLIARDI ◽

F ALBIERO ◽

R CICCIARELLO ◽

...

Keyword(s):

Natural Killer Cell ◽

Natural Killer ◽

Mhc Class I ◽

Nk Cell ◽

Killer Cell ◽

Class I ◽

Cell Recognition ◽

Cell Target ◽

Mhc Class I Molecules

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A research-driven approach to the identification of novel natural killer cell deficiencies affecting cytotoxic function

Blood ◽

10.1182/blood.2019000925 ◽

2020 ◽

Vol 135 (9) ◽

pp. 629-637

Author(s):

Michael T. Lam ◽

Emily M. Mace ◽

Jordan S. Orange

Keyword(s):

Natural Killer Cell ◽

Nk Cells ◽

Natural Killer ◽

Nk Cell ◽

Killer Cell ◽

Cell Development ◽

Impact Testing ◽

Primary Immune Deficiency ◽

Cell Cytotoxicity ◽

Nk Cell Cytotoxicity

Abstract Natural killer cell deficiencies (NKDs) are an emerging phenotypic subtype of primary immune deficiency. NK cells provide a defense against virally infected cells using a variety of cytotoxic mechanisms, and patients who have defective NK cell development or function can present with atypical, recurrent, or severe herpesviral infections. The current pipeline for investigating NKDs involves the acquisition and clinical assessment of patients with a suspected NKD followed by subsequent in silico, in vitro, and in vivo laboratory research. Evaluation involves initially quantifying NK cells and measuring NK cell cytotoxicity and expression of certain NK cell receptors involved in NK cell development and function. Subsequent studies using genomic methods to identify the potential causative variant are conducted along with variant impact testing to make genotype-phenotype connections. Identification of novel genes contributing to the NKD phenotype can also be facilitated by applying the expanding knowledge of NK cell biology. In this review, we discuss how NKDs that affect NK cell cytotoxicity can be approached in the clinic and laboratory for the discovery of novel gene variants.

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Adrenergic β1- and β1+2-receptor blockade suppress the natural killer cell response to head-up tilt in humans

Journal of Applied Physiology ◽

10.1152/jappl.1997.83.5.1492 ◽

1997 ◽

Vol 83 (5) ◽

pp. 1492-1498 ◽

Cited By ~ 13

Author(s):

M. Klokker ◽

N. H. Secher ◽

P. Madsen ◽

M. Pedersen ◽

B. K. Pedersen

Keyword(s):

Natural Killer Cell ◽

Nk Cells ◽

Natural Killer ◽

Cell Response ◽

Nk Cell ◽

Killer Cell ◽

Saline Control ◽

Receptor Blockade ◽

Natural Killer Cell Response ◽

Head Up Tilt

Klokker, M., N. H. Secher, P. Madsen, M. Pedersen, and B. K. Pedersen. Adrenergic β1- and β1+2-receptor blockade suppress the natural killer cell response to head-up tilt in humans. J. Appl. Physiol. 83(5): 1492–1498, 1997.—To evaluate stress-induced changes in blood leukocytes with emphasis on the natural killer (NK) cells, eight male volunteers were followed during three trials of head-up tilt with adrenergic β1- (metoprolol) and β1+2- (propranolol) blockade and with saline (control) infusions. The β1- and β1+2-receptor blockade did not affect the appearance of presyncopal symptoms, but the head-up tilt induced a transient lymphocytosis that was abolished by β1+2-receptor blockade but not by β1-receptor blockade. Head-up tilt also resulted in delayed neutrophilia, which was insensitive to β-receptor blockade. Lymphocyte subset analysis revealed that the head-up tilt resulted in a twofold increase in the percentage and absolute number of CD3−/CD16+and CD3−/CD56+NK cells in peripheral blood and that this increase was partially blocked by metoprolol and abolished by propranolol. The NK cell activity on a per NK cell basis did not change during head-up tilt, indicating that the cytotoxic capability of NK cells recruited to circulation is unchanged. The data suggest that the head-up tilt-induced lymphocytosis was due mainly to CD16+and CD56+NK cells and that their recruitment to the blood was inhibited by β1- and especially β1+2-receptor blockade. Thus stress-induced recruitment of lymphocytes, and of NK cells in particular, is mediated by epinephrine through activation of β-receptors on the lymphocytes.

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β-Endorphin and natural killer cell cytolytic activity during prolonged exercise. Is there a connection?

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.275.6.r1725 ◽

1998 ◽

Vol 275 (6) ◽

pp. R1725-R1734 ◽

Cited By ~ 1

Author(s):

G. A. Gannon ◽

S. G. Rhind ◽

M. Suzui ◽

J. Zamecnik ◽

B. H. Sabiston ◽

...

Keyword(s):

Natural Killer Cell ◽

Natural Killer ◽

Nk Cell ◽

Block Design ◽

Killer Cell ◽

Cytolytic Activity ◽

Opioid Antagonist ◽

Moderate Intensity ◽

Moderate Intensity Exercise ◽

Cell Counts

This study was designed to test whether a single 50-mg dose of the opioid antagonist naltrexone hydrochloride, ingested 60 min before 2 h of moderate-intensity exercise (i.e., 65% peak O2consumption), influenced the exercise-induced augmentation of peripheral blood natural killer cell cytolytic activity (NKCA). Ten healthy male subjects were tested on four occasions separated by intervals of at least 14 days. A rested-state control trial was followed by three double-blind exercise trials [placebo (P), naltrexone (N), and indomethacin] arranged according to a random block design. The indomethacin exercise trial is discussed elsewhere (S. G. Rhind, G. A. Gannon, P. N. Shek, and R. J. Shepherd. Med. Sci. Sports Exerc. 30: S20, 1998). For both the P and N trials, plasma levels of β-endorphin were increased ( P < 0.05) at 90 and 120 min of exercise but returned to resting (preexercise) levels 2 h postexercise. CD3−CD16+CD56+NK cell counts and NKCA were significantly ( P < 0.05) elevated at each 30-min interval of exercise compared with correspondingly timed resting control values. However, there were no differences in NK cell counts or NKCA between P and N trials at any time point during the two trials. Changes in NKCA reflected mainly changes in NK cell count ( r = 0.72; P < 0.001). The results do not support the hypothesis that the enhancement of NKCA during prolonged submaximal aerobic exercise is mediated by β-endorphin.

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Natural killer cells suppress human erythroid stem cell proliferation in vitro

Blood ◽

10.1182/blood.v63.2.260.260 ◽

1984 ◽

Vol 63 (2) ◽

pp. 260-269 ◽

Cited By ~ 66

Author(s):

KF Mangan ◽

ME Hartnett ◽

SA Matis ◽

A Winkelstein ◽

T Abo

Keyword(s):

Stem Cell ◽

Natural Killer Cell ◽

Nk Cells ◽

Natural Killer ◽

Nk Cell ◽

Killer Cell ◽

Human Natural Killer Cell ◽

Percoll Density Gradient Centrifugation

Abstract To determine the role of natural killer (NK) cells in the regulation of human erythropoiesis, we studied the effects of NK-enriched cell populations on the in vitro proliferation of erythroid stem cells at three different levels of maturation (day 14 blood BFU-E, day 5–6 marrow CFU-E, and day 10–12 marrow BFU-E). NK cells were enriched from blood by Percoll density gradient centrifugation and by fluorescence- activated cell sorting (FACS), using the human natural killer cell monoclonal antibody, HNK-1. The isolated enriched fractions were cocultured with autologous nonadherent marrow cells or blood null cells and erythropoietin in a methylcellulose erythroid culture system. Cells from low-density Percoll fractions (NK-enriched cells) were predominantly large granular lymphocytes with cytotoxic activity against K562 targets 6–10-fold greater than cells obtained from high- density Percoll fractions (NK-depleted cells). In coculture with marrow nonadherent cells (NA) at NK:NA ratios of 2:1, NK-enriched cells suppressed day 5–6 CFU-E to 62% (p less than 0.025) of controls, whereas NK-depleted cells slightly augmented CFU-E to 130% of controls (p greater than 0.05). In contrast, no suppression of day 10–12 marrow BFU-E was observed employing NK-enriched cells. The NK CFU-E suppressor effects were abolished by complement-mediated lysis of NK-enriched cells with the natural killer cell antibody, HNK-1. Highly purified HNK- 1+ cells separated by FACS suppressed marrow CFU-E to 34% (p less than 0.025) and marrow BFU-E to 41% (p less than 0.025) of controls. HNK- cells had no significant effect on either BFU-E or CFU-E growth. NK- enriched cells were poor stimulators of day 14 blood BFU-E in comparison to equal numbers of NK-depleted cells or T cells isolated by E-rosetting (p less than 0.01). Interferon boosting of NK-enriched cells abolished their suboptimal burst-promoting effects and augmented their CFU-E suppressor effects. These studies provide evidence for a potential regulatory role of NK cells in erythropoiesis. The NK suppressor effect is maximal at the level of the mature erythroid stem cell CFU-E. These findings may explain some hypoproliferative anemias that develop in certain NK cell-activated states.

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