Sugiura H, Ishikura H, Omi M, Kaji M, Iwai K, Kishimoto T, Takahashi T, Kimura C, Kato H, Yoshiki T
Department of Pathology, Hokkaido University, School of Medicine, Sapporo, Japan.
Pathol Int. 1994 Sep;44(9):688-96. doi: 10.1111/j.1440-1827.1994.tb02948.x.
Eight pancreas carcinoma cell lines of duct cell origin (PCI-6, 10, 19, 24, 35, 43, 55, and 64) were established. Using one of these lines, PCI-24, human umbilical vein endothelial cells (HUVEC), and several recombinant cytokines, conditions and specificity of anti-PCI LAK induction were investigated, with the focus on a search for lymphokine-activated killer (LAK) activity that differentiates neoplastic (PCI) from non-neoplastic (HUVEC) cells. Interferon-gamma (IFN-gamma), IFN-alpha, IL-4, IL-6, and IL-7, but not tumor necrosis factor-alpha (TNF-alpha) or IL-1 beta, induced a weak LAK activity against PCI-24, whereas IL-2-induced (1000 U/mL) LAK exhibited a far more potent cytotoxicity. When these cytokines were added at the suboptimal dose IL-2 (100 U/mL), no significant augmentation in LAK activity was induced. Staphylococcal protein A (SpA) induced LAK activity as potent as that seen with IL-2 (1000 U/mL). Both IL-2-induced and SpA-induced LAK had a potent, dose-dependent cytotoxicity against HUVEC. HUVEC inhibited both IL-2- and SpA-induced LAK cytotoxicity against PCI-24 to almost the same extent as seen with PCI-24. Thus, two potent LAK-inducers did not generate LAK activity that differentiates neoplastic from non-neoplastic cells. Thus, in vitro cytotoxicity of LAK against non-neoplastic endothelial cells is unavoidable when handling cytokines in LAK induction.
建立了8种导管细胞来源的胰腺癌细胞系（PCI - 6、10、19、24、35、43、55和64）。使用其中一种细胞系PCI - 24、人脐静脉内皮细胞（HUVEC）以及几种重组细胞因子，研究了抗PCI LAK诱导的条件和特异性，重点是寻找能够区分肿瘤性（PCI）和非肿瘤性（HUVEC）细胞的淋巴因子激活的杀伤细胞（LAK）活性。γ干扰素（IFN - γ）、IFN - α、IL - 4、IL - 6和IL - 7可诱导针对PCI - 24的微弱LAK活性，但肿瘤坏死因子 - α（TNF - α）或IL - 1β则不能，而IL - 2诱导（1000 U/mL）的LAK表现出更强的细胞毒性。当以次优剂量的IL - 2（100 U/mL）添加这些细胞因子时，未诱导出LAK活性的显著增强。葡萄球菌蛋白A（SpA）诱导的LAK活性与IL - 2（1000 U/mL）诱导的相当。IL - 2诱导和SpA诱导的LAK对HUVEC均有强大的、剂量依赖性的细胞毒性。HUVEC对IL - 2和SpA诱导的针对PCI - 24的LAK细胞毒性的抑制程度与PCI - 24几乎相同。因此，两种强效的LAK诱导剂并未产生能够区分肿瘤性和非肿瘤性细胞的LAK活性。因此，在LAK诱导过程中处理细胞因子时，LAK对非肿瘤性内皮细胞的体外细胞毒性是不可避免的。
