HEMATOPOIESIS-PROMOTING ACTIVITY OF RAT-LIVER BILIARY EPITHELIAL-CELLS - INVOLVEMENT OF A CELL-SURFACE MOLECULE, LIVER-REGULATING PROTEIN

Stromal cell lines from bone marrow and other blood-forming organs inc luding fetal liver have been found to support hematopoiesis. In this p aper, we demonstrate that rat liver biliary epithelial cells (RLEC), m ost likely originating from primitive bile ductules, are able to suppo rt long-term hematopoietic cell growth as well as burst-forming unit-e rythroid (BFU-E) and colony-forming unit-granulocyte/macrophage (CFU-G M) production. RLEC have previously been shown to express a cell surfa ce molecule named liver-regulating protein (LRP), which is involved in the long-term maintenance of hepatocyte functions in a coculture syst em. In addition, LRP-like molecules have been found in spleen, thymus, lymph nodes, and peripheral blood cells. In the present study, we fou nd that hematopoietic cells and several stromal cell types from bone m arrow were LRP-positive, and immunoprecipitation revealed polypeptides similar to those found in RLEC. We then investigated the biological r ole of LRP on hematopoiesis using short-term RLEC and bone marrow stro mal cell culture systems. Addition of specific anti-LRP antibody to bo th systems reduced hematopoietic cell proliferation and committed prog enitor production, whereas it did not directly affect the clonal proli feration and maturation of these progenitors in methylcellulose assays . Moreover, using diffusible chamber cultures that suppress direct con tacts with hematopoietic cells, we observed low cell growth and no eff ect of monoclonal antibody (mAb) L8 treatment. All these results stron gly argue for a cell proximity signal mediated by RLEC and bone marrow stromal cells and for the involvement of LRP-like molecules in this s ignal in liver and bone marrow hematopoietic function.