Liver granulomas in schistosomiasis: mast cell-dependent induction of SCF expression in hepatic stellate cells is mediated by TNF-alpha.

Mast cell proliferation, survival, and differentiation are under control of the surrounding stroma and are largely mediated by the stem cell factor (SCF). Mast cells are abundant in liver fibrosis and are proposed to be causally related with its persistence and intensity through secretion of fibrogenic cytokines. In normal adult liver, local connective tissue cells (stellate cells) do not constitutively express SCF. We studied primary cultures of stellate cells obtained from fibrogranulomatous reactions elicited in mouse liver by schistosomal infection. We have shown that the SCF expression can be induced in vitro by co-culture with mast cells and this induction was dependent on the release of tumor necrosis factor alpha (TNF-alpha). Because SCF induces in mast cells proliferation and release of both fibrogenic factors and TNF-alpha, the described interaction between liver stroma and mast cells represents an auto-stimulatory loop, which may explain the progressive and persistent character of liver fibrosis associated with chronic inflammations or infections. Granulomatous reactions in liver elicited by chronic schistosomiasis sustain a local production of inflammatory cells, and this extramedular myelopoiesis is potentially also dependent on the induction of SCF expression in the liver stellate cells.