HYDROGEN-PEROXIDE IS INVOLVED IN LYMPHOCYTE-ACTIVATION MECHANISMS TO INDUCE ANGIOGENESIS

T-lymphocytes from tumour-bearing mice are able to trigger the angioge nic cascade. Since it is known that tumour growth produces reactive ox ygen species (ROS), the aim of this study was to evaluate the role of hydrogen peroxide (H2O2) on the activation of lymphocytes and their in duction of this vascular response. Studies on lymphocytes, stimulated in vitro by ROS to induce angiogenesis, showed that only the enzyme ca talase (CAT) could block the activation. The incubation of normal lymp hocytes with H2O2 stimulated these cells to induce angiogenesis. The a dministration of H2O2 or an oxidative stress-producing drug (doxorubic in) to normal mice activated in vivo angiogenesis. In tumour-bearing m ice, high levels of lipid peroxidation products were observed in the s pleen, but not in the liver or kidney. Moreover, when the ROS scavenge r enzyme activities (superoxide dismutase (SDM) and CAT) were determin ed, we observed low CAT activity in normal spleens, reflected in a hig h SDM/CAT ratio, when compared to liver or kidney values. We also show ed an increasing value of the SDM/CAT ratio with tumour growth. These results strongly suggest that H2O2 could be involved in the mechanisms of lymphocyte activation and their induction of angiogenesis during t umour growth. (C) 1997 Elsevier Science Ltd.