22 O - Taurine enhances macrophage-mediated cytotoxicity via increased arginase release

Abstract

Taurine is the most abundant intracellular free amino acid present in inflammatory cells. Preliminary experiments have demonstrated that Taurine abrogates IL-2-mediated endothelial cell injury by NK and LAK cells while enhancing NK and LAK anti-tumour function, therefore the aim of this study was to investigate the tumouricidal potential of Taurine-stimulated murine peritoneal macrophages (MOs). CD-I mice were randomised into two study groups. Group A received an i.p. injection of Taurine (200mg/kg) and group B received a saline control. Peritoneal cells were harvested after 24hrs and the Mos were isolated by adherence. Cytotoxicity ± lysine [(L) a known arginase inhibitor] was assessed using Cr 51 against the Wehi (W) and P815 (P) tumour targets. Nitric oxide (NO) and arginase release were also assessed as markers of cytotoxic activity. CONTRAL TAURINE Cytotoxicity Vs W (%) 35.0 ± 17.2 @ 75.l ± l5.4 * @ Cytotoxicity + L Vs W (%) 4.9 ± 2.5 6.1 ±1.0 Cytotoxicity Vs P (%) 28.5 ± 8.9 @ 68.3 ± 14.3 * @ Cytotoxicity + L Vs P (%) 9.5 ± 6.3 20.1 ± 10.6 NO umols/ug prot. 1.8 ± 0.7 1.4 ± 0.6 Arginase umols/ug prot/hr 118.6 ± 319 180.6 ± 32.8 * Stats.=Students t-test * p a p MOs stimulated by Taurine have enhanced tumouricidal activity against both tumour targets and this effect is abrogated when arginase release is blocked by the competitive inhibitor L-lysine. NO levels are decreased. however. arginase release is increased indicating a preferential uptake of L-arginine for the enhancement of MO tumouricidal activity. Modulation of this anti-tumour pathway may play an important role in host anti-tumour defense.