A. Corlu et al., HEMATOPOIESIS-PROMOTING ACTIVITY OF RAT-LIVER BILIARY EPITHELIAL-CELLS - INVOLVEMENT OF A CELL-SURFACE MOLECULE, LIVER-REGULATING PROTEIN, Experimental hematology, 26(5), 1998, pp. 382-394
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.