Taurine attenuates recombinant interleukin-2-activated, lymphocyte-mediated endothelial cell injury

Abstract

BACKGROUND. Recombinant interleukin-2 (rIL-2) immunotherapy is limited by mi-Nicola M. Finnegan, B.A.Mod. crovascular endothelial cell (EC)-targeted injury. The interaction between rIL-2-H. Paul Redmond, F.R.C.S.I. activated lymphoid cells and EC is a possible mechanism of this systemic toxicity. David J. Bouchier-Hayes, F.R.C.S.I. Taurine, a b-amino acid, is known to have several physiologic actions, including the modulation of calcium homeostasis. The aims of this study were to analyze Department of Surgery, Royal College of Sur-the effects of taurine on rIL-2-activated, lymphocyte-mediated EC and tumor cell geons in Ireland, Beaumont Hospital, Dublin, Ireland. 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.

Investigating thein vitroeffect of taurine on the infant lymphocytes by sister chromatid exchange

“…18 It has been shown to stimulate T and B lymphocytes in response to mitogens and reported to play a dual role in recombinant interleukin-2 immunotherapy, due to its ability to reduce the vascular injury associated with this therapy while enhancing its antineoplastic activity. 10 The result of the present study showed that the physiological concentration of taurine decreases MMC-induced SCE in infants lymphocytes. We suggest that the high levels of taurine found in the human milk may induce protecting effects of BF against DNA damage and malignancy.…”

“…Taurine is reported to be the most abundant free amino acid in lymphocytes (44%) 10 . Its concentration in leukocytes is reported to be between 20–50 mM 11 .…”

“…Taurine is also reported to be an antimutagen in the Ames Salmonella tester strain assay 18 . It has been shown to stimulate T and B lymphocytes in response to mitogens and reported to play a dual role in recombinant interleukin‐2 immunotherapy, due to its ability to reduce the vascular injury associated with this therapy while enhancing its antineoplastic activity 10 …”

Protection of bleomycin-induced fibrosis and inflammation by taurine

“…The protective effects of taurine may be explained by its detoxification of hypochlorous acid, a potent oxidant that can cause extensive tissue damage. However, recent evidence from our laboratories [10][11][12][13][14][15][16] and others [17][18][19] demonstrates that taurine chloramine (Tau-Cl), produced from highly toxic hypochlorous acid and taurine, is thought to be pivotal in regulating inflammation. Our previous data demonstrate that Tau-Cl inhibits proinflammatory mediators such as NO and TNF-α in a variety of both primary macrophages and cultured macrophagelike lines from rodents [10,13].…”

Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure.

“…Such antidote effects of taurine or high capacity for taurine uptake into the cells (or conversely harmful effects of taurine depletion) have i.a . been found against alcohol (23–40), against the analgesic and fever-depressing drug acetaminophen (also called paracetamol) (41–44), against the aminoglycoside antibacterial drug gentamicin (45–47), against the immunosuppressant drug cyclosporine A (48, 49), against the anticancer drugs cisplatin (50–54), doxorubicin (also called adriamycin) (55–62), bleomycin (63–78), methotrexate (79) and taumustine (80), against the cytokine interleukin-2 (IL-2), which is used for immunotherapy of cancer (81–84), against the estrogen receptor modulator tamoxifen, which is used in therapy of breast cancer (85–87), against the antiarrhythmic drug amiodarone (88), against the beta -adrenergic agonists isoproterenol (55) and isoprenaline (89–92), against nicotine (93–95), against oxidized low-density lipoprotein (LDL) (96), against oxidized fish oil (97), against high glucose levels (96, 98–110), against fructose (111–122), against galactose (123), against advanced glycation end-products (AGEs) (100, 124, 125), against homocysteine (126–130), against the anti-inflammatory drugs ibuprofen (131) and indomethacin (132, 133), against the herbicide paraquat (65, 134, 135), against carbon tetrachloride (136–149), against menadione (150), against 1,4-naphtoquinone (137, 139), against hydrazine (137, 139), against trinitrobenzene sulfonic acid (151, 152), against acrylonitrile (153), against perchloroethylene (154), against methylene dianiline (155), against arsenic (156–164), against cadmium (…”