Prostaglandin E2-mediated suppression of murine lymphokine-activated killer cell activity generated from tumor-bearing hosts by interferon-gamma.
The effect of mouse recombinant interferon-gamma (IFN-gamma) on murine lymphokine-activated killer (LAK) cell activity was investigated using a natural killer-resistant, LAK-sensitive, spontaneously developed, weakly immunogenic, syngeneic murine mammary adenocarcinoma, a tumor model mimicking that of human disease. When all of the splenocytes prepared from tumor-bearing mice were cultured with recombinant interleukin-2 (IL-2) and IFN-gamma, LAK cell activity was suppressed in an IFN-gamma dose-dependent manner. An increase in the prostaglandin E2 (PGE2) content in the corresponding culture media was detected, as was IFN-gamma dose dependent. The suppression of generation of LAK cell activity by IFN-gamma was abrogated, accompanied by the elimination of the increase in PGE2 content, when plastic dish and nylon wool-treated nonadherent macrophage-depleted splenocytes were used. These results indicated that IL-2-induced LAK cell activity generated from the splenocytes of tumor-bearing mice was suppressed by IFN-gamma, and that PGE2 secreted from the macrophages of the splenocyte cultures served as the mediator in this IFN-gamma dose-dependent suppression of IL-2-induced LAK cell activity.
Nakajima
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Department of Diagnostic Immunology Research and Biochemistry, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.
Chu
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D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D014408:Biomarkers, Tumor; D015232:Dinoprostone / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000187:drug effects; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D011994:Recombinant Proteins; D007371:Interferon-gamma; D015232:Dinoprostone