Ortaldo J R, Ransom J R, Sayers T J, Herberman R B
J Immunol. 1986 Nov 1;137(9):2857-63.
Previous results that were obtained by using supernatants from the co-culture of human peripheral blood lymphocytes and the natural killer susceptible cell line K562 strongly inhibited the growth of various tumor cell lines. No correlation was observed between the susceptibility of the target cell lines to growth inhibition and to lysis by natural killer cells. Rather the spectrum of cytostatic activity and the characteristics of the soluble factor were similar to those of leukoregulin (LRG), a recently described lymphokine. Because of the recent availability of recombinant tumor necrosis factor (TNF) and lymphotoxin (LT), we compare the target selectivity and mechanism of action of these (TNF, LT, LRG) factors with natural killer cytotoxic factor (NKCF). The pattern of target cell susceptibility to growth inhibition or cytolysis by the factors were quite distinct from the pattern observed when cells were exposed to NKCF. Furthermore, antibodies to rLT or rTNF had no effect on LRG cytostasis or NKCF lysis, arguing against a requirement for or synergistic interaction with low levels of LT or TNF. Some of the targets susceptible to LRG were growth inhibited but were not lysed, thereby distinguishing it from NKCF. Furthermore, LRG cytostasis was not inhibited by mannose-6-PO4 or rabbit antibodies to granule cytolysin, both of which block natural killer cytotoxic factor. Therefore, LRG appears to be a cytostatic factor produced by large granular lymphocytes in response to K562 that is distinct from NKCF, TNF, and LT. In addition, NKCF, rLT, rTNF, and LRG, although having cytotoxic/cytostatic activity, are distinct functional factors and may represent a family of lytic factors.
先前通过使用人外周血淋巴细胞与自然杀伤敏感细胞系K562共培养的上清液所获得的结果强烈抑制了各种肿瘤细胞系的生长。未观察到靶细胞系对生长抑制的敏感性与自然杀伤细胞的裂解之间存在相关性。相反，细胞生长抑制活性谱和可溶性因子的特性与最近描述的一种淋巴因子——白细胞调节素（LRG）相似。由于最近可获得重组肿瘤坏死因子（TNF）和淋巴毒素（LT），我们将这些（TNF、LT、LRG）因子与自然杀伤细胞毒性因子（NKCF）的靶标选择性和作用机制进行了比较。这些因子对靶细胞生长抑制或细胞溶解的敏感性模式与细胞暴露于NKCF时观察到的模式截然不同。此外，抗rLT或rTNF的抗体对LRG的细胞生长抑制作用或NKCF的细胞溶解作用均无影响，这表明不需要低水平的LT或TNF，也不存在与之的协同相互作用。一些对LRG敏感的靶细胞生长受到抑制，但未被裂解，从而将其与NKCF区分开来。此外，甘露糖-6-磷酸或抗颗粒溶素的兔抗体均不能抑制LRG的细胞生长抑制作用，而这两种物质均可阻断自然杀伤细胞毒性因子。因此，LRG似乎是大颗粒淋巴细胞响应K562产生的一种细胞生长抑制因子，它不同于NKCF、TNF和LT。此外，NKCF、rLT、rTNF和LRG虽然具有细胞毒性/细胞生长抑制活性，但它们是不同的功能因子，可能代表了一类裂解因子。
