Pilaro A M, Taub D D, McCormick K L, Williams H M, Sayers T J, Fogler W E, Wiltrout R H
Laboratory of Experimental Immunology, PRI/DynCorp, NCI-FCRDC, Frederick, MD 21702.
J Immunol. 1994 Jul 1;153(1):333-42.
Isolated murine splenic NK cells and the cultured murine endothelioma cell line, eEND2, were used to study the effects of cytokines on NK cell/endothelial cell adhesion. Treatment of eEND2 cells with TNF-alpha induced a marked increase (four- to sevenfold) in adherence of NK cells, as compared with control cultures of endothelioma cells or eEND2 cells treated with IL-1 alpha or IL-6. TNF-alpha induction of NK cell adherence to eEND2 was dose dependent with rapid kinetics, reaching a maximum at concentrations between 10 and 1000 U/ml after a 2-h incubation. TNF-alpha treatment of L929 fibroblasts or CL-2 hepatoma cells did not result in increased NK cell adhesion. The concentration range of TNF-alpha that was found to maximally augment NK cell adhesion to eEND2 also induced NK cell chemokinetic activity. The relevance of these in vitro results was subsequently analyzed in vivo. Initial studies confirmed that a single dose of polyinosinic-polycytidylic acid and poly-L-lysine stabilized in carboxymethyl cellulose (poly-ICLC), augmented hepatic NK activity and resulted in a 2.2-fold increase in the number of liver-associated NK cells. Concomitant treatment of mice with a TNF-alpha neutralizing antisera eliminated both the hepatic influx of NK cells and the increase in poly-ICLC-induced liver NK activity. These results suggest that TNF-alpha is a principal cytokine involved in the in vivo recruitment and localization of parenchymal NK cells after treatment with a biological response modifier, and that this regulation seems to occur via alterations in NK cell/endothelial cell interactions.
分离的小鼠脾脏自然杀伤（NK）细胞和培养的小鼠内皮瘤细胞系eEND2，用于研究细胞因子对NK细胞/内皮细胞黏附的影响。与用白细胞介素-1α（IL-1α）或白细胞介素-6（IL-6）处理的内皮瘤细胞对照培养物或eEND2细胞相比，用肿瘤坏死因子-α（TNF-α）处理eEND2细胞可使NK细胞的黏附显著增加（4至7倍）。TNF-α诱导NK细胞黏附到eEND2细胞是剂量依赖性的，动力学迅速，孵育2小时后，在10至1000 U/ml的浓度下达到最大值。用TNF-α处理L929成纤维细胞或CL-2肝癌细胞不会导致NK细胞黏附增加。发现能最大程度增强NK细胞黏附到eEND2细胞的TNF-α浓度范围也诱导了NK细胞的化学趋化活性。随后在体内分析了这些体外结果的相关性。初步研究证实，单剂量的聚肌苷酸-聚胞苷酸和羧甲基纤维素稳定化的聚-L-赖氨酸（聚肌胞苷酸，poly-ICLC）可增强肝脏NK活性，并使肝脏相关NK细胞数量增加2.2倍。用TNF-α中和抗血清同时处理小鼠，消除了NK细胞的肝脏流入以及聚肌胞苷酸诱导的肝脏NK活性增加。这些结果表明，TNF-α是在用生物反应调节剂处理后参与实质NK细胞体内募集和定位的主要细胞因子，并且这种调节似乎是通过NK细胞/内皮细胞相互作用的改变而发生的。
