IN-VIVO INDUCTION OF APOPTOSIS (PROGRAMMED CELL-DEATH) IN MOUSE THYMUS BY ADMINISTRATION OF LIPOPOLYSACCHARIDE

In vivo administration of bacterial lipopolysaccharide to mice induced DNA fragmentation in the thymus. Fragmented DNA was confirmed by agarose gel electrophoresis and laser flow cytometry. DNA fragmentation was predominantly detected in the thymus of young mice, while it was undetectable in the spleen, bone marrow, and lymph nodes. DNA fragmentation in the thymus was roughly dependent on the dose of lipopolysaccharide injected and reached the peak about 18 h after the injection. The addition of lipopolysaccharide to in vitro cultures of thymocytes did not cause DNA fragmentation, suggesting that lipopolysaccharide was unable to induce apoptosis of thymocytes directly. The injection of lipopolysaccharide induced no significant DNA fragmentation in adrenalectomized mice. The injection of anti-tumor necrosis factor alpha antibody together with lipopolysaccharide partially inhibited the appearance of DNA fragmentation in the thymus. On the basis of the fact that DNA fragmentation is one of the characteristics typical in apoptotic cell death, it was suggested that lipopolysaccharide could induce apoptosis in the mouse thymus in vivo. This apoptosis in the thymus might be mediated mainly by the adrenal hormones, but it is likely that tumor necrosis factor alpha might also participate in it.