Concanavalin A simultaneously primes liver hematopoietic and epithelial progenitor cells for parallel expansion during liver regeneration after partial hepatectomy in mice

Liver hematopoietic progenitor cells (LHPC) and liver epithelial progenitor cells (LEPC) share a remarkable number of growth and differentiation-contr olling receptor-ligand signaling systems. These likely account for the abil ity of the liver to support hematopoiesis in fetal life, and possibly for s uggestions that LHPC can differentiate into hepatocytes. In these experimen ts, the kinetics and magnitude of LHPC and LEPC activation and expansion we re studied by using a concanavalin A (Con A) liver injury model followed by partial hepatectomy (PH), Studies were performed in interleukin 6-deficien t (IL-6(-/-)) mice and wild-type (IL-6(+/+)) controls, which show equal sus ceptibility to Con A-induced injury, because IL-6/gp130 signaling has been implicated in both LHPC and LEPC expansion. Con A pretreatment primed LHPC and LEPC for a rapid and parallel expansion after PH in IL-6(+/+) mice, whi ch was significantly blunted and delayed in the IL-6(-/-) mice. Exogenous I L-6 given immediately before PH after Con A, augmented both LHPC and LEPC e xpansion in the IL-6(-/-) mice. Thus, the proinflammatory cytokine IL-6, co mmonly produced in liver injury and inflammatory disease, is an important g rowth factor involved in the expansion of LHPC and LEPC. This observation h as implications for both hepatic carcinogenesis and transplantation.