Okada M, Sagawa T, Tominaga A, Kodama T, Hitsumoto Y
Department of Clinical Laboratory Technology, Ehime College of Health Science, Japan.
Immunology. 1996 Sep;89(1):158-64. doi: 10.1046/j.1365-2567.1996.d01-716.x.
We have tried to identify the cytotoxic effectors in platelet-mediated tumour cell killing, using two tumour cell lines K562 (a chronic myelogenic leukaemic cell line) and LU99A (a lung cancer cell line), which are both sensitive to platelet cytotoxicity. Cyclo-oxygenase inhibitors, acetylsalicylic acid (ASA) and indomethacin, effectively inhibited the platelet-mediated killing of K562 cells, but not that of LU99A cells. In contrast, inhibitors of the nitric oxide (NO) pathway. NG-nitro-1-arginine (L-NA), haemoglobin and methylene blue, reduced the cytotoxic activity of platelets against LU99A, but not against K562. Synthetic analogues of platelet cyclo-oxygenase products thromboxane A2/ prostaglandin H2(TXA2/PGH2) exerted cytotoxicity against K562 cells but not against LU99A cells. Electron microscopic study showed that TXA2/PGH2 analogues induced bleb formation and disruption of the plasma membrane of K562 cells. K562 cells enhanced the production of TXA2 by platelets, as inferred from the accumulation of thromboxane B2 (TXB2), a spontaneous hydrolysis product of TXA2. LU99A cells had no such effects. These results indicate that platelets kill these two tumour cell lines through different mechanisms. In K562, the cyclooxygenase products TXA2/PGH2 possibly play a significant role but in LU99A the NO pathway seems to be involved.
我们试图利用两种对血小板细胞毒性敏感的肿瘤细胞系K562（一种慢性粒细胞白血病细胞系）和LU99A（一种肺癌细胞系）来确定血小板介导的肿瘤细胞杀伤中的细胞毒性效应物。环氧化酶抑制剂乙酰水杨酸（ASA）和吲哚美辛可有效抑制血小板介导的K562细胞杀伤，但对LU99A细胞无效。相反，一氧化氮（NO）途径抑制剂NG-硝基-L-精氨酸（L-NA）、血红蛋白和亚甲蓝可降低血小板对LU99A的细胞毒性活性，但对K562细胞无效。血小板环氧化酶产物血栓素A2/前列腺素H2（TXA2/PGH2）的合成类似物对K562细胞具有细胞毒性，但对LU99A细胞无效。电子显微镜研究表明，TXA2/PGH2类似物可诱导K562细胞形成泡状结构并破坏其质膜。从TXA2的自发水解产物血栓素B2（TXB2）的积累推断，K562细胞可增强血小板TXA2的产生。LU99A细胞则无此作用。这些结果表明，血小板通过不同机制杀伤这两种肿瘤细胞系。在K562细胞中，环氧化酶产物TXA2/PGH2可能起重要作用，但在LU99A细胞中，NO途径似乎参与其中。
