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 inflammatory 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 levels of virus-induced cytokines and, because of a sparing effect on their phagocytic cells, retention of the phagocytic inflammatory response. A component of phagocytic activation is the initiation of the oxidative burst, 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 decreased cytoprotective capabilities. Relative to 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 supplemented with conditioned medium from MOT, 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 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 of AIDS-KS.
Mallery
S R
SR
Department of Dentistry, College of Dentistry, Ohio State University, Columbus 43210-1241.
Ng-Bautista
C L
CL
Lantry
L E
LE
Ness
G M
GM
Hegtvedt
A K
AK
Lazo
A
A
Bailer
R T
RT
Hout
B L
BL
Stephens
R E
RE
Brierley
G P
GP
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D002374:Catalase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D006801:Humans; D009711:Nucleotides / Q000032:analysis; D012514:Sarcoma, Kaposi / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D009711:Nucleotides; D002374:Catalase; D005978:Glutathione