CULTURED AIDS-RELATED KAPOSIS-SARCOMA CELLS RETAIN A PROLIFERATIVE BIOENERGETIC PROFILE BUT DEMONSTRATE REDUCED CYTOPROTECTIVE CAPABILITIES

Features of AIDS-related Kaposi's sarcoma (AIDS-KS), such as the multi focal presentation at mucosal and epidermal sites subjected to trauma, suggest that AIDS-KS is initially a reactive hyperplasia that subsequ ently progresses to a neoplasia. It is recognized that there is an ass ociation between sustained inflammatory states and the subsequent deve lopment of neoplasia (e.g., ulcerative colitis/colonic adenocarcinoma) . Furthermore, patients who develop AIDS-KS experience both a constant immune stimulation due to sustained high levels of virus-induced cyto kines and, because of a sparing effect on their phagocytic cells, rete ntion of the phagocytic inflammatory response. A component of phagocyt ic activation is the initiation of the oxidative burst, resulting in t he generation of reactive oxygen species (ROS), which can be mutagenic to host cells if released beyond the phagolysosome and not inactivate d. Our results demonstrate that cultured AIDS-KS cells possess decreas ed cytoprotective capabilities. Relative to either dermal fibroblasts, or human microvascular endothelial cells (HMECs), AIDS-KS cells conta ined significantly lower levels of glutathione, a tripeptide integral in both cytoprotection and maintenance of cellular thiol status. While HMECs increased catalase activity during culture in the cytokine-rich KS milieu (control medium supplemented with conditioned medium from M OT, an HTLV II-infected cell line), AIDS-KS cells demonstrated reduced catalase function under these conditions. Furthermore, HMEC cultures showed an inherent biochemical responsiveness, by increasing catalase activity following exposure to exogenous H2O2. In contrast, the catala se activity of AIDS-KS cells decreased following H2O2 challenge. Our r esults show that an inherent deficiency in cellular cytoprotection is present in AIDS-KS cells and suggest that oxidant stress may function in the development and progression of AIDS-KS. (C) 1994 Wiley-Liss, In c.