Antiviral and tumoricidal activities of alginate-stimulated macrophages are mediated by different mechanisms.
Macrophages play an important role in host defenses by killing tumors and virus infections and producing secretory products. High mannuronic acid (HMA) containing alginate was examined to determine the mechanisms by which HMA-activated macrophages resist infection with HSV-1 and inhibit the growth of tumor cells. The ability of macrophages to resist infection with HSV-1 or to inhibit the growth of tumor cells was assessed following treatment with HMA alginate in the presence of either antibodies to various cytokines or inhibitors/scavengers of toxic macrophage products. Only antibodies to IFN-alpha/beta were able to abrogate the protective effects of HMA alginate in macrophages infected with HSV-1, suggesting that the antiviral activity induced by this immunomodulator was mediated by the production of IFN-beta. In contrast, anti-TNF-alpha, anti-IFN and inhibitors of nitric oxide and reactive oxygen species were all able to partially abrogate HMA-induced cytostatic activity, suggesting that multiple mechanisms are involved in macrophage cytostasis. These results indicate that the HMA-induced intrinsic antiviral and extrinsic cytotoxic activites are mediated by different mechanisms.
Son
Eun-Wha
EW
Korea Institute of Science and Technology Information 206-9, Cheongryangri-Dong, Dongdaemun-Gu, Seoul 130-742, Korea.
Rhee
Dong-Kwon
DK
Pyo
Suhkneung
S
D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000378:metabolism*; D000998:Antiviral Agents / Q000276:immunology / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D020723:Glucuronic Acid / Q000494:pharmacology*; D006603:Hexuronic Acids / Q000494:pharmacology*; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D000464:Alginates; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D006603:Hexuronic Acids; D016899:Interferon-beta; D020723:Glucuronic Acid; C008324:mannuronic acid