Cultured AIDS-related Kaposi's sarcoma cells retain a proliferative bioenergetic profile but demonstrate reduced cytoprotective capabilities

Features of AIDS‐related Kaposi's sarcoma (AIDS‐KS), such as the multifocal presentation at mucosal and epidermal sites subjected to trauma, suggest that AIDS‐KS is initially a reactive hyperplasia that subsequently progresses to a neoplasia. It is recognized that there is an association between sustained states and the subsequent development of neoplasia (e.g., ulcerative colitis/colonic adenocarcinoma). Furthermore, patients who develop AIDS‐KS experience both a constant immune stimulation due to sustained high levelsof virus‐induced cytokines and, because of a sparing effect on their phagoctic cells, retention of the phagocytic inflammatory response. A component of phygocytic activation is the initiation of the oxidative brust, resulting in the generation of reactive oxygen species (ROS), which can be mutagenic to host cells if released beyond the phagolysosome and not inactivated. Our results demonstrate that cultured AIDS‐KS cells possess drcreased cytoprotective capabilities. Relativeto either dermal fibroblasts, or human microvascular endothelial cells (HMECs), AIDS‐KS cells contained 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 supplement with conditioned medium from MOT, an TLV II‐infected cell line), AIDS‐KS cells demonstrated reduced catalase function under these conditions. Furthermore, HMEC cultures showed in inherent biochemical responsiveness, by increasing catalase activity following exposure to exaogenous H2(O2). In contrast, the catalase activity of AIDS‐KS cells decreased following (H2O2) challenge. Our results 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 AIDS‐KS.