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A fetal sheep liver extract containing immunostimulatory substances including LPS acts as leukocyte activator in cells of LPS responder and non responder mice.
Purified fractions from a fetal sheep liver extract (FSLE) were investigated, in a murine model, for induction of leukocyte stimulating activities. The fractions FSLE-1 and FSLE-2 induced splenocyte proliferation in vitro in C57Bl/10ScSn (LPS responder) mice comparable to LPS, and in C57Bl/10ScCr (LPS non responder) mice. They also stimulated the release of nitrogen radicals in bone marrow-derived macrophages (BMDM) from several mouse inbred strains including both C57Bl/10ScSn and C57Bl/10ScCr mice. Stimulation of NO production could be blocked by L-NMMA, an inhibitor of iNOS, and enhanced by the simultaneous addition of IFN-gamma. Moreover, stimulation of macrophages by FSLE-1 and FSLE-2 induced a cytostatic effect of the activated macrophages for Abelson 8-1 tumor cells. The stimulatory activity of the purified fractions is partially due to trace amounts of LPS derived from the fetal liver extract which was enriched during purification. Our results may help to explain the beneficial effect of the extract in patients which has been observed clinically.
Animals, Cell Line, Tumor/drug effects, Cell Line, Tumor/metabolism, Cell Proliferation/drug effects, Coculture Techniques, Dose-Response Relationship, Drug, Immunologic Factors/isolation & purification, Immunologic Factors/pharmacology, Interferon-gamma/pharmacology, Leukocytes/drug effects, Lipopolysaccharides/isolation & purification, Lipopolysaccharides/pharmacology, Liver/chemistry, Liver/embryology, Macrophages/drug effects, Macrophages/metabolism, Mice, Mice, Inbred C57BL, Nitric Oxide/metabolism, Nitric Oxide Synthase Type II/antagonists & inhibitors, Sheep/embryology, Spleen/cytology, Spleen/drug effects, omega-N-Methylarginine/pharmacology
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