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Two mechanisms for platelet‐mediated killing of tumour cells: one cyclo‐oxygenase dependent and the other nitric oxide dependent
Author(s) -
OKADA M.,
SAGAWA T.,
TOMINAGA A.,
KODAMA T.,
HITSUMOTO Y.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1996.d01-716.x
Subject(s) - thromboxane a2 , k562 cells , chemistry , cytotoxicity , platelet , cytotoxic t cell , cell culture , nitric oxide , biochemistry , microbiology and biotechnology , pharmacology , cell , biology , immunology , receptor , in vitro , genetics , organic chemistry
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, N G ‐nitro‐ L ‐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 A 2 /prostaglandin H 2 (TXA 2 /PGH 2 ) exerted cytotoxicity against K562 cells but not against LU99A cells. Electron microscopic study showed that TXA 2 /PGH 2 analogues induced bleb formation and disruption of the plasma membrane of K562 cells. K562 cells enhanced the production of TXA 2 by platelets, as inferred from the accumulation of thromboxane B 2 (TXB 2 ), a spontaneous hydrolysis product of TXA 2 . LU99A cells had no such effects. These results indicate that platelets kill these two tumour cell lines through different mechanisms. In K562, the cyclo‐oxygenase products TXA 2 /PGH 2 possibly play a significant role, but in LU99A the NO pathway seems to be involved.