Heat shock suppresses human NK cell cytotoxicity via regulation of perforin
Heat shock suppresses human NK cell cytotoxicity via regulation of perforin
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DOI：
10.1080/02656730701822087
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发表时间：
2007-12-01
影响因子：
3.1
通讯作者：
Kai, Hirofumi
中科院分区：
文献类型：
--
作者：
Harada, Hideki;Murakami, Toru;Kai, Hirofumi
人体NK细胞是一种重要的免疫监视淋巴细胞，对热具有高度敏感性，但其对热的反应性质和热调控机制尚不清楚。本文研究了体外热休克和体内热疗对人NK细胞毒性的影响。从健康志愿者获得的人外周血单个核细胞（PBMC）进行体外热休克（42℃，1 h）。接受有意热疗（42℃，1小时）的癌症患者的PBMC也被获得。测定这些样品的NK细胞溶解活性。在体外热休克5h时，NK细胞的细胞毒性下调，但在热休克24h时，NK细胞毒性与对照组相当。此外，我们观察到NK细胞的细胞溶解颗粒perform的mRNA和蛋白表达水平在热休克后5h和24h受到与NK细胞毒性相似的方式的调节。热调节涉及CD56（暗）NK细胞亚群中的穿孔蛋白，而不涉及CD56（亮）NK细胞亚群中的穿孔蛋白。热休克既没有诱导细胞死亡，也没有改变一些NK激活受体和粘附分子的表达。此外，肿瘤患者在42℃下全身热疗1小时也能抑制NK细胞的细胞毒性，但在热疗1周后恢复到基础水平。体外和体内热休克可暂时抑制人NK细胞的细胞毒性。
Human natural killer (NK) cell, which is an important lymphocyte for immune surveillance, is highly sensitive to heat, but the nature of its response to and its mechanistic regulation by heat remain unclear. Here we determined the effect of in vitro heat shock and in vivo hyperthermia on human NK cell cytotoxicity. Human peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers were subjected to heat shock in vitro (42 degrees C, 1 h). PBMC from cancer patients receiving intentional hyperthermia (42 degrees C, 1 h) for cancer therapy were also obtained. NK cytolytic activity was determined in these samples. NK cell cytotoxicity was down-regulated by heat shock in vitro at 5h, but at 24h after heat shock, the NK cytotoxicity was comparable to that with its respective control. Furthermore, we observed that the mRNA and protein expression levels of perform, which is the cytolytic granule of NK cells, were regulated by heat shock in a similar manner as NK cytotoxicity at 5h and at 24h after heat shock. Heat regulation involved the perforin protein in CD56(dim) but not in CD56(bright) NK cell subset. Heat shock neither induced cell death nor altered the expression of some NK activating receptors and adhesion molecules. Moreover, whole-body hyperthermia at 42 degrees C for 1 h of cancer patients also suppressed the cytotoxicity of NK cells but recovered to basal level 1 week after hyperthermia. Heat shock in vitro and in vivo temporarily represses the cytotoxicity of human NK cells.