title: Macrophage-mediated suppression of natural killer cell activity in mice bearing Lewis lung carcinoma.
abstract: The natural killer (NK) cell cytotoxic capacity of C57BL/6 mice with implantation of Lewis lung carcinoma (LLC) was quantitated during tumor growth. The NK activity became suppressed at 1 week of tumor growth and remained suppressed. The mechanisms for the suppression during the first 3 weeks of tumor growth included secretion of prostaglandin E2 (PGE2) by both the LLC tumor and host macrophages. With tumor growth, plasma PGE2 concentrations progressively increased. Oral administration of indomethacin to tumor-bearing mice prevented the rise in serum PGE2 concentrations and the suppression of NK activity. Cultured LLC cells and splenic macrophages isolated from mice during the first 3 weeks of tumor growth secreted increased amounts of PGE2. Macrophages from tumor-bearer spleen cells were shown to suppress NK activity. Depletion of these macrophages restored the NK activity, and addition of these macrophages to normal spleen cells resulted in an indomethacin-sensitive suppression of the NK response. The mechanisms of suppression in mice bearing large tumors were different than those observed with smaller tumors. With a large tumor burden, the plasma PGE2 concentrations declined. Indomethacin treatment did not prevent the suppression of NK activity, and depletion of splenic macrophages did not restore NK cytotoxicity.
authors.forename: M R
authors.initials: MR
authors.lastname: Young
authors.forename: E
authors.initials: E
authors.lastname: Wheeler
authors.forename: M
authors.initials: M
authors.lastname: Newby
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic; D015232:Dinoprostone; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D011458:Prostaglandins E / Q000097:blood / Q000378:metabolism; D013154:Spleen / Q000276:immunology
chemical_list: D011458:Prostaglandins E; D015232:Dinoprostone