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 administration of macrophage activators. The proliferation of macrophages and extrathymic T cells is spontaneously induced in the liver of autoimmune MRL-lpr/lpr mice, and deeply involved in the development of disease. To study the role of Kupffer cell activation in the induction of hematopoiesis and lymphocyte proliferation in the liver, we histologically analysed the kinetic and spatial relationship between Kupffer cells and hematopoietic cells or lymphocytes. At 5 weeks of age before the onset of disease, there were no appreciable histological changes in the liver. At 7 weeks, Kupffer cells had slightly increased in number, while hematopoietic islands were not yet detected. When disease had fully developed at 14 weeks, Kupffer cells were considerably increased in number and size, and exhibited numerous lysosomes. Hematopoietic cells of erythroid and myeloid series frequently appeared in the sinusoid, and lay in close apposition to Kupffer cells. Promyelocytes further migrated into the space of Disse to cluster there, being surrounded by the stellate cells (or fat-storing cells) and hepatocytes. After maturation, metamyelocytes and mature granulocytes were released into the sinusoidal circulation. Mitotic figures were detected in the cells of both erythroid and myeloid series. Lymphocytes proliferated in various sites such as in the sinusoid lumen, the space of Disse, and interlobular connective tissue, whether associated or not with Kupffer cells. The present results indicate that erythropoiesis, granulopoiesis, and lymphocyte proliferation are induced in the liver of MRL-lpr/lpr mice and are closely associated with Kupffer cell activation.