In vivo suppression of NK cell cytotoxicity by stress and surgery: glucocorticoids have a minor role compared to catecholamines and prostaglandins.
In vivo suppression of NK cell cytotoxicity by stress and surgery: glucocorticoids have a minor role compared to catecholamines and prostaglandins.
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DOI：
10.1016/j.bbi.2013.12.007
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发表时间：
2014-03
影响因子：
15.1
通讯作者：
Ben-Eliyahu, Shamgar
中科院分区：
文献类型：
--
作者：
Rosenne, Ella;Sorski, Liat;Shaashua, Lee;Neeman, Elad;Matzner, Pini;Levi, Ben;Ben-Eliyahu, Shamgar
大多数体外和离体研究表明，糖皮质激素对NK细胞的细胞毒性（NKCC）有深刻的抑制作用;而据报道，儿茶酚胺和野牡丹素既能抑制也能增强NKCC。然而，方法上的考虑阻碍了我们从这些发现中推断出这些因子的内源性释放对体内NKCC水平的影响及其对NK依赖性对活体人类或动物病理学的抗性的影响的能力。在这里，我们使用了一种体内方法，敏感性和特异性地反映了活的F344大鼠中的NKCC，基于NK敏感性肿瘤细胞（MADB 106）的肺清除率，并基于比较NK完整和NK耗尽大鼠之间的效果。为了研究皮质酮、肾上腺素和肾上腺素的作用，我们将这些因素给予大鼠，或拮抗它们在不同应激范式或手术后的内源性释放。结果表明，内源性或外源性升高的皮质酮水平可以抑制体内NKCC水平，但仅在某些条件下，并且大多数是继发于肾上腺素的NK抑制作用。具体而言，皮质酮诱导的NKCC抑制（i）仅在长时间暴露于压力下发生，但不是短时间暴露于压力下，主要发生在雄性动物中;（ii）小于肾上腺素的显著影响;（iii）主要归因于皮质酮诱导的肾上腺素或/和肾上腺素作用增强;（iv）通过拮抗肾上腺素或/和肾上腺素完全消除。总体而言，这些发现明显限制了应激/手术诱导的皮质酮释放在NKCC体内抑制中的意义，并强调了阻断肾上腺素或/和肾上腺素作为克服这种免疫抑制作用的有效且临床可行的方法。
Most in vitro and ex-vivo studies indicate a profound suppression of NK cell cytotoxicity (NKCC) by glucocorticoids; while catecholamines and prostaglandins were reported both to suppress and to enhance NKCC. However, methodological considerations hinder our ability to deduce from these findings to the impact of endogenous release of these factors on in vivo levels of NKCC and their implications to NK-dependent resistance to pathologies in living humans or animals. Here we used an in vivo approach that sensitively and specifically reflects NKCC in living F344 rats, based on lung clearance of NK-sensitive tumor cells (MADB106), and based on comparing effects between NK-intact and NK-depleted rats. To study the role of corticosterone, epinephrine, and prostaglandins, we administered these factors to rats, or antagonized their endogenous release following different stress paradigms or surgery. The results indicated that endogenous or exogenous elevated corticosterone levels can suppress in vivo NKCC levels, but only under some conditions, and mostly secondarily to the NK-suppressing impact of epinephrine. Specifically, corticosterone-induced NKCC suppression occurred (i) only under prolonged, but not short exposure to stress, and mainly in males; (ii) was smaller than the prominent impact of epinephrine; (iii) was mostly ascribed to corticosterone-induced potentiation of the effects of epinephrine or/and prostaglandins; and (iv) was completely abolished through antagonizing epinephrine or/and prostaglandins. Overall, these findings markedly limit the significance of stress/surgery-induced corticosterone release in the in vivo suppression of NKCC, and highlight the blockade of epinephrine or/and prostaglandins as effective and clinically feasible approaches to overcome such immuno-suppressive effects.
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影响因子：
2.4
作者：
Ben-Eliyahu, S;Shakhar, G;Shakhar, K
通讯作者：
Shakhar, K
影响因子：
3
作者：
Hiraki, Shuhichi;Ono, Satoshi;Mochizuki, Hidetaka
通讯作者：
Mochizuki, Hidetaka
影响因子：
9
作者：
Goldfarb, Yael;Sorski, Liat;Ben-Eliyahu, Shamgar
通讯作者：
Ben-Eliyahu, Shamgar
影响因子：
4.4
作者：
Glasner, Ariella;Avraham, Roi;Ben-Eliyahu, Shamgar
通讯作者：
Ben-Eliyahu, Shamgar
DOI：
10.1165/ajrcmb.19.5.3103
发表时间：
1998-11-01
影响因子：
6.4
作者：
Broug-Holub, E;Persoons, JHA;Kraal, G
通讯作者：
Kraal, G