Stimulatory effects of neopterin on hematopoiesis in vitro are mediated byactivation of stromal cell function

The pteridine neopterin (NP) was shown to be produced by monocytes and is k nown to be a useful marker of immunological activation, although, its biolo gical activity is still unclear. Recently, we found that intravenous admini stration of NP increased the numbers of blood leukocytes, and granulocyte-m acrophage progenitor cells (CFU-GM) in the bone marrow and spleens of mice. In order to elucidate the mechanism whereby NP stimulates hematopoiesis, t he effects of NP on hematopoietic stem cell proliferation and differentiati on in vitro were studied using a long-term bone marrow culture (LTMC) syste m with cloned stromal cell line, MS-5, Adding NP to the LTMC increased the numbers of cells in total, CFU-GM and colony-forming unit in spleen (CFU-S) . NP also increased the number of CFU-GM in a soft agar culture system, but it did not enhance CFU-GM colony formation when target bone marrow cells w ere semi-purified (T, B and adherent cell-depleted bone marrow cells) and c ultured in this system, suggesting that NP did not directly affect the prol iferation of hematopoietic progenitors. Conditioned medium obtained from NP -treated stromal cells had much greater colony-stimulating activity than th at obtained from untreated stromal cells. Furthermore, NP treatment stimula ted the production of IL-6 and GM-CSF by stromal cells, All these findings suggest that NP stimulates hematopoietic cell proliferation and differentia tion in vitro by activating stromal cell function. Copyright (C) 1998 John Wiley & Sons, Ltd.