Pollock R E, Lotzová E, Stanford S D
Department of General Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
J Immunol. 1989 Nov 15;143(10):3396-403.
NK cell cytotoxicity may provide an important first line of defense against the implantation of circulating tumor emboli. Previously we reported that murine hind limb amputation induces a rapid and marked impairment of perioperative NK cell cytotoxicity that is associated with increased metastatic activity compared to unmanipulated tumor-bearing controls. Because tumor emboli are systemically discharged in patients undergoing solid tumor resection, we thought it pertinent to begin examining the mechanism underlying the perioperative impairment of murine NK cell cytotoxicity. Studies presented in this report suggest that the mechanism of impairment is multifactorial and includes the surgical stress-induced expansion of splenic erythroblasts that successfully compete with NK cells for YAC-1 target binding sites. In addition, although there is no surgically mediated decrease in splenic NK cell content (as defined morphologically, phenotypically, and functionally), there is an acute decrease in maximal NK cell recycling capacity. An accurate understanding of the mechanisms mediating perioperative impairment of NK cell cytotoxicity may be important in the future development of NK-specific perioperative immunomodulation strategies.
自然杀伤（NK）细胞的细胞毒性可能为抵御循环肿瘤栓子的植入提供重要的第一道防线。此前我们报道，与未接受手术操作的荷瘤对照组相比，小鼠后肢截肢会导致围手术期NK细胞细胞毒性迅速且显著受损，这与转移活性增加有关。由于实体瘤切除患者体内的肿瘤栓子会被全身排出，我们认为有必要开始研究小鼠围手术期NK细胞细胞毒性受损的潜在机制。本报告中的研究表明，这种受损机制是多因素的，包括手术应激诱导的脾成红细胞扩增，这些细胞成功地与NK细胞竞争YAC-1靶标结合位点。此外，虽然手术并未介导脾NK细胞数量的减少（从形态学、表型和功能上定义），但NK细胞的最大再循环能力会急剧下降。准确理解介导围手术期NK细胞细胞毒性受损的机制，对于未来开发NK特异性围手术期免疫调节策略可能具有重要意义。
