In Vitro Effect of Neopterin on Splenic Mast Cell Development in Senescence Accelerated Mice (SAM)

Neopterin is produced by monocytes and is a useful biomarker of inflammatory responses. We found that neopterin enhances granulopoiesis, but suppresses B-lymphopoiesis triggered by the positive- and negative regulations of cytokines produced by stromal cells in mice. Furthermore, neopterin suppressed the colony formation of mast cell progenitor (CFU-mast) from bone marrow cells in in vitro culture system. In this study, neopterin was also found to regulate the proliferation and differentiation of splenic CFU-mast in vitro as observed in that from bone marrow, which was confirmed in the mouse model of senescent stromal-cell impairment (SCI). In non-SCI mice (=less senescent stage of SCI mice), neopterin also decreased the number of colonies of interleukin-3 (IL-3)-dependent mast-cell progenitor cells (CFU-mast) from unfractionated spleen cells, but not that from the lineage-negative (fractionated) spleen cell population without stromal cells in a semisolid in vitro culture system. In contrast, in a case of SCI mice, the treatment with neopterin did not decrease the number of colonies of IL-3-dependent mast-cell progenitor cells (CFU-mast) from unfractionated spleen cells. These results suggest that, firstly, neopterin decrease the number of colonies of IL-3-dependent CFU-mast by stimulating splenic stromal cells, and secondly, such neopterin function becomes declined during senescence because of an impaired stromal-cell function.