Mechanism of replacement of non-parenchymal liver cells (NPLC) in murine radiation chimeras.

The mechanism of cell replacement of non-parenchymal liver cells (NPLC) was investigated in an attempt to answer the question: to what extend are NPLC replaced by proliferation of local resident cells and to what extend by cells originating from the bone-marrow. The bone-marrow of mice was used, and H2k positive cells from F1 (B10.BR X B10.D2) hybrid mice were transplanted into irradiated H2k negative parent animals. Their NPLC were isolated and tested immunocytochemically with a monoclonal anti-H2k antibody for the presence of H2k positive cells. During the whole of the experiment (from the 5th to the 20th week following transplantation) H2k positive cells (macrophages and non-macrophages) were present, and made up an average of nearly one third of the NPLC. The H2k positive (immigrant) non-macrophages showed essentially more active DNA synthesis than these H2k negative cells. To increase cell turnover, we injected one group of animals with endotoxin. At the time of maximum replacement, more than 50% of the NPLC (macrophages and non-macrophages) were recruited from cells of bone-marrow origin. Note-worthy here was the proportionate level of the H2k positive macrophages (more than 70% of all liver macrophages). The DNA synthesis of both the H2k positive macrophages and non-macrophages was more than twice that of the H2k negative NPLC during the regeneration process following administration of endotoxin. Our observations suggest that the bone-marrow contributes significantly to the replacement of macrophages and non-macrophages of NPLC in both health and disease.