Suppression of macrophage function in AK-5 tumor transplanted animals: role of TGF-beta1.
Transforming growth factor-beta 1 (TGF-beta1), a multifunctional cytokine secreted by various cell types has been implicated in diverse physiologic and pathophysiologic functions, including immunological, inflammatory, and neoplastic processes. AK-5 tumor cells when injected intraperitoneally grow as ascites, causing 100% mortality. Peritoneal macrophages cocultured with AK-5 cells, in vitro showed specific suppression of tumoricidal function. We report that AK-5 cells secrete the latent form of TGF-beta1, which is converted to its active homodimeric form, causing suppression of the secretion of cytocidal molecule by macrophages thereby inhibiting their cytotoxic capabilities. When macrophages are cocultured with AK-5 cells in the presence of antibodies against TGF-beta1 or the receptor II for TGF-beta, there is significant recovery in the secretion of nitric oxide and macrophage cytotoxic potential. These results suggest a major role for TGF-beta produced by the tumor cells, in the immune escape mechanisms adopted by the AK-5 tumor cells.
Mitra
Roshni
R
Centre for Cellular and Molecular Biology, Tumor Immunology, Uppal Road, Hyderabad 500007, India.
Khar
Ashok
A
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009589:Nitrogen Oxides / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2
D000906:Antibodies; D009589:Nitrogen Oxides; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat