Kupffer cell activation and hematopoiesis in the liver of autoimmune MRL-lpr/lpr mice

Hematopoiesis can be induced in the adult murine liver by the administratio n of macrophage activators. The proliferation of macrophages and extrathymi c T cells is spontaneously induced in the liver of autoimmune MRL-lpr/lpr m ice, and deeply involved in the development of disease. To study the role o f Kupffer cell activation in the induction of hematopoiesis and lymphocyte proliferation in the liver, we histologically analysed the kinetic and spat ial relationship between Kupffer cells and hematopoietic cells or lymphocyt es, At 5 weeks of age before the onset of disease, there were no appreciabl e histological changes in the liver. At 7 weeks, Kupffer cells had slightly increased in number, while hematopoietic islands were not yet detected. Wh en disease had fully developed at 14 weeks, Kupffer cells were considerably increased in number and size, and exhibited numerous lysosomes. Hematopoie tic cells of erythroid and myeloid series frequently appeared in the sinuso id, and lay in close apposition to Kupffer cells. Promyelocytes further mig rated into the space of Disse to cluster there, being surrounded by the ste llate cells (or fat-storing cells) and hepatocytes. After maturation, metam yelocytes and mature granulocytes were released into the sinusoidal circula tion. Mitotic figures were detected in the cells of both erythroid and myel oid series. Lymphocytes proliferated in various sites such as in the sinuso id lumen, the space of Disse, and interlobular connective tissue, whether a ssociated or not with Kupffer cells. The present results indicate that eryt hropoiesis, granulopoiesis, and lymphocyte proliferation are induced in the liver of MRL-lpr/lpr mice and are closely associated with Kupffer cell act ivation.