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Taurine attenuates recombinant interleukin‐2‐activated, lymphocyte‐mediated endothelial cell injury
Author(s) -
Finnegan Nicola M.,
Redmond H. Paul,
BouchierHayes David J.
Publication year - 1998
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19980101)82:1<186::aid-cncr24>3.0.co;2-y
Subject(s) - medicine , recombinant dna , taurine , lymphocyte , immunology , interleukin , interleukin 2 , endothelial stem cell , cytokine , biochemistry , biology , in vitro , amino acid , gene
BACKGROUND Recombinant interleukin‐2 (rIL‐2) immunotherapy is limited by microvascular endothelial cell (EC)‐targeted injury. The interaction between rIL‐2‐activated lymphoid cells and EC is a possible mechanism of this systemic toxicity. Taurine, a β‐amino acid, is known to have several physiologic actions, including the modulation of calcium homeostasis. The aims of this study were to analyze the effects of taurine on rIL‐2‐activated, lymphocyte‐mediated EC and tumor cell cytotoxicity and to investigate the mechanisms of its action. METHODS IL‐2‐activated cytotoxicity, mediated by peripheral blood mononuclear cells, against susceptible tumor cell lines and against EC (fresh EC and an EC cell line) in the presence of taurine was assessed. The effects of taurine on lymphocyte [Ca 2+ ] i were assessed by flow cytometry, and the effects of taurine on granzyme activity were assessed by spectrophotometry. RESULTS The authors' findings indicated that the addition of taurine significantly reduced rIL‐2‐activated EC cytotoxicity mediated by natural killer cells, without reducing antitumor response. Taurine was also shown to reduce significantly EC lysis mediated by lymphokine‐activated killer (LAK) cells, while also significantly increasing tumor cytotoxicity. The authors demonstrated the importance of calcium in the role played by taurine in lymphocyte‐mediated cytotoxicity and found that LAK [Ca 2+ ] i following conjugation to EC was enhanced by taurine. They also found that taurine enhanced Ca 2+ ‐dependent granzyme exocytosis from LAK cells. CONCLUSIONS These findings indicate that taurine may play a dual role in rIL‐2 immunotherapy, due to its ability to reduce the vascular injury associated with this therapy while enhancing its antineoplastic activity. Cancer 1998;82:186‐99. © 1998 American Cancer Society.