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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 stromalcell function.

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