HEMATOPOIETIC CAPACITY OF COLONY-FORMING CELLS MOBILIZED IN HEPATIC INFLAMMATORY REACTIONS AS COMPARED TO THAT OF NORMAL BONE-MARROW CELLS

Chronic inflammatory periovular granulomatous reactions elicited in li ver by schistosomal infection are a site of active myelopoiesis. We qu antified the colony-forming cells (CFCs) in granulomas and found that the whole liver contains a number of CFCs roughly equivalent to 50% of a femur. Clonogenic analysis showed the presence of committed as well as pluripotent and totipotent CFCs. Long-term Dexter-type cultures sh owed that the granuloma-derived totipotent CFCs do not have self-renew al capacity. Hence, they did not correspond functionally to haematopoi etic stem cells, despite the fact that the stroma established by adher ent cells harvested from granulomas had the capacity to sustain long-t erm proliferation of bone-marrow-derived haematopoietic stem cells. We conclude that myelopoietic cytokines produced by inflammatory reactio ns in schistosomiasis elicit mobilization of bone marrow CFCs into the circulation, which can settle in hepatic granulomas. This environment may induce their proliferation and differentiation, but not their sel f renewal, sustaining temporary production of myeloid cell lineages wh ich nevertheless depends upon cell renewal from the bone marrow pool o f haematopoietic precursors.