Hydrogen peroxide is involved in lymphocyte activation mechanisms to induce angiogenesis

T-lymphocytes from tumour-bearing mice are able to trigger the angiogenic cascade. Since it is known that tumour growth produces reactive oxygen species (ROS), the aim of this study was to evaluate the role of hydrogen peroxide (H2O2) on the activation of lymphocytes and their induction of this vascular response. Studies on lymphocytes, stimulated in vitro by ROS to induce angiogenesis, showed that only the enzyme catalase (CAT) could block the activation. The incubation of normal lymphocytes with H2O2 stimulated these cells to induce angiogenesis. The administration of H2O2 or an oxidative stress-producing drug (doxorubicin) to normal mice activated in vivo angiogenesis. In tumour-bearing mice, high levels of lipid peroxidation products were observed in the spleen, but not in the liver or kidney. Moreover, when the ROS scavenger enzyme activities (superoxide dismutase (SDM) and CAT) were determined, we observed low CAT activity in normal spleens, reflected in a high SDM/CAT ratio, when compared to liver or kidney values. We also showed 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 tumour growth.