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 agar ose gel electrophoresis and laser flow cytometry. DNA fragmentation wa s predominantly detected in the thymus of young mice, while it was und etectable in the spleen, bone marrow, and lymph nodes. DNA fragmentati on in the thymus was roughly dependent on the dose of lipopolysacchari de injected and reached the peak about 18 h after the injection. The a ddition of lipopolysaccharide to in vitro cultures of thymocytes did n ot cause DNA fragmentation, suggesting that lipopolysaccharide was una ble to induce apoptosis of thymocytes directly. The injection of lipop olysaccharide induced no significant DNA fragmentation in adrenalectom ized 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 fr agmentation is one of the characteristics typical in apoptotic cell de ath, it was suggested that lipopolysaccharide could induce apoptosis i n the mouse thymus in vivo. This apoptosis in the thymus might be medi ated mainly by the adrenal hormones, but it is likely that tumor necro sis factor alpha might also participate in it.