Mechanisms of the Antimetastatic Effects of Anticoagulant Drugs: Dependence on Natural Killer (NK) Cell Activity

2019 ◽  
pp. 37-45
Author(s):  
E. Gorelik ◽  
E. Bere ◽  
R. B. Herberman
1983 ◽  
Vol 55 (2) ◽  
pp. 305-309 ◽  
Author(s):  
Yasuhiro Yoda ◽  
Tsukasa Abe ◽  
Akio Tashiro ◽  
Shinsaku Hirosawa ◽  
Kenichi Kawada ◽  
...  

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yan Feng ◽  
Yan Li ◽  
Ying Zhang ◽  
Bo-Hao Zhang ◽  
Hui Zhao ◽  
...  

Abstract Background Brain ischemia compromises natural killer (NK) cell-mediated immune defenses by acting on neurogenic and intracellular pathways. Less is known about the posttranscriptional mechanisms that regulate NK cell activation and cytotoxicity after ischemic stroke. Methods Using a NanoString nCounter® miRNA array panel, we explored the microRNA (miRNA) profile of splenic NK cells in mice subjected to middle cerebral artery occlusion. Differential gene expression and function/pathway analysis were applied to investigate the main functions of predicted miRNA target genes. miR-1224 inhibitor/mimics transfection and passive transfer of NK cells were performed to confirm the impact of miR-1224 in NK cells after brain ischemia. Results We observed striking dysregulation of several miRNAs in response to ischemia. Among those miRNAs, miR-1224 markedly increased 3 days after ischemic stroke. Transfection of miR-1224 mimics into NK cells resulted in suppression of NK cell activity, while an miR-1224 inhibitor enhanced NK cell activity and cytotoxicity, especially in the periphery. Passive transfer of NK cells treated with an miR-1224 inhibitor prevented the accumulation of a bacterial burden in the lungs after ischemic stroke, suggesting an enhanced immune defense of NK cells. The transcription factor Sp1, which controls cytokine/chemokine release by NK cells at the transcriptional level, is a predicted target of miR-1224. The inhibitory effect of miR-1224 on NK cell activity was blocked in Sp1 knockout mice. Conclusions These findings indicate that miR-1224 may serve as a negative regulator of NK cell activation in an Sp1-dependent manner; this mechanism may be a novel target to prevent poststroke infection specifically in the periphery and preserve immune defense in the brain.


1995 ◽  
Vol 79 (3) ◽  
pp. 732-737 ◽  
Author(s):  
S. J. Won ◽  
M. T. Lin

The effects of different ambient temperatures (Ta) on the splenic natural killer (NK) cell activity, effector-target cell conjugation activity, and NK cell numbers were assessed in male inbred C3H/HeNCrj mice (7–10 wk old). The splenic NK cytotoxic activities were examined in a 4-h 51Cr release assay in mouse spleen cells that were obtained 1, 2, 4, 8, or 16 days after exposure to Ta of 22, 4, or 35 degrees C. The percentage of conjugating lymphocytes was calculated by counting the number of single lymphocytes bound to single target cells per 400 effector cells. The numbers of NK cells were expressed by the percentage of 5E6-positive cells. The 5E6 identifies only a subset of NK cells. It was found that the splenic NK cell activity, the effector-target cell conjugation activity, or the NK cell number began to fall 1 day after cold (Ta 4 degrees C) or heat (Ta 35 degrees C) stress. After a 16-day period of either cold or heat exposure, the fall in the splenic NK cell activity, the effector-target cell conjugation activity, or the number of 5E6-positive subsets of NK cells was still evident. Compared with those of the control group (Ta 22 degrees C), the cold-stressed mice had higher adrenal cortisol concentration and lower colonic temperature, whereas the heat-stressed animals had higher adrenal cortisol concentration and higher colonic temperature during a 16-day period of thermal exposure. However, neither cold nor heat stress affected both the body weight gain and the spleen weight in our mice.


1998 ◽  
Vol 275 (4) ◽  
pp. R1227-R1231
Author(s):  
H. B. Nielsen ◽  
N. H. Secher ◽  
M. Kappel ◽  
B. K. Pedersen

This study evaluated whether N-acetylcysteine (NAC) attenuates the reduced lymphocyte proliferation and natural killer (NK) cell activity responses to exercise in humans. Fourteen oarsmen were double-blind randomized to either NAC (6 g daily for 3 days) or placebo groups. During 6-min “all-out” ergometer rowing, the concentration of lymphocytes in the peripheral blood increased, with no significant difference between NAC and placebo as reflected in lymphocyte subsets: CD4+, CD8+, CD16+, and CD19+ cells. The phytohemagglutinin-stimulated lymphocyte proliferation decreased from 9,112 ± 2,865 to 5,851 ± 1,588 cpm ( P < 0.05), but it was not affected by NAC. During exercise, the NK cell activity was elevated from 17 ± 3 to 38 ± 4% and it decreased to 7 ± 1% below the resting value 2 h into recovery. Yet, when evaluated as lytic units per CD16+ cell, the NK cell activity decreased during and after exercise without a significant effect of NAC. We conclude that NAC does not attenuate the reduction in lymphocyte proliferation and NK cell activity associated with intense exercise.


1984 ◽  
Vol 75 (7) ◽  
pp. 1124-1133
Author(s):  
Masamichi Hayakawa ◽  
Kazuhiko Nagakura ◽  
Macoto Hata ◽  
Toshi Fujioka ◽  
Hiroshi Nakamura ◽  
...  

1994 ◽  
Vol 10 (3) ◽  
pp. 149-154 ◽  
Author(s):  
Andrew Campbell ◽  
Nachman Brautbar ◽  
Aristo Vojdani

We have previously shown that natural killer (NK) cell activity is significantly suppressed in patients with silicone breast implants. These patients were symptomatic and the suppression of natural killer cell activity was associated with additional significant immunological abnormalities (Vojdani et al, 1992a). Our studies have recently been confirmed by Smith et al. (1994), who described natural killer cell activity suppression following exposure to silicone gel, and reversal upon removal of the gel. This study has been designed to evaluate natural killer cell activities in symptomatic women with silicone breast implants and again after explantation of the implants. Each patient served as her own control. Our findings show a marked significant increase in previously suppressed natural killer cell activity in 50% of the patients. In the other 50%, no change or suppressed NK activity was observed. These findings are compatible with recent studies in experimental animals, which show that administration of silicone reduces natural killer cell activity, and that this is reversible upon removal of the silicone. Since NK cells are important in the control of tumor cell growth, we propose here that patients with reduced NK cell activity are at a higher risk of developing cancer, a concept recently described in experimental animals (Potter et al., 1994; Salhon et al, 1994).


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