Department of Functional Morphology, School of Medicine, Nihon University, Tokyo 173–8610, Japan.
Biol Pharm Bull. 2011;34(10):1533-41. doi: 10.1248/bpb.34.1533.
Mast-cell-development in the bone-marrow (BM) and the spleen is restrictedly controlled by stromal-cells which produce positive-regulators such as stem cell factor (SCF), and negative-regulators such as transforming growth factor-β (TGF-β). How the balance between positive- and negative-regulation is achieved or maintained by stromal-cells is not well understood. We intravenously injected 5-fluorouracil (5-FU) and lipopolysaccharide (LPS) into C3H/HeN mice to disrupt mast-cell-development in order to reveal mechanisms of mast-cell-regulation. 5-FU treatment induces a rapid decrease in the number of mast-cell-progenitor (colony-forming unit (CFU)-mast) cells in the BM and spleen, followed by rapid recovery of CFU-mast numbers. Expression of the SCF gene is one-fiftieth the level of that of TGF-β during the steady-state in BM and spleen. After 5-FU treatment, SCF mRNA levels in the BM markedly increased, approaching TGF-β mRNA levels, whereas SCF levels in the spleen showed limited oscillations whose increases paralleled those in TGF-β levels. In contrast, LPS treatment induces a rapid decrease in CFU-mast number in the BM and a rapid increase in of CFU-mast number in the spleen. After LPS treatment, SCF mRNA levels in the BM markedly decreased, whereas SCF levels in the spleen remained unchanged. These results suggest that regulation of mast-cell-development is dominated by negative-signals in the BM and spleen during the steady-state, and, under biostress-conditions such as 5-FU and LPS treatment, the balance between positive- and negative-regulation can be changed in the BM but not in the spleen. The difference in the regulation of mast-cell-development in the BM versus the spleen probably reflects the different roles of tissue-specific stromal-cells.
骨髓（BM）和脾脏中的肥大细胞发育受到基质细胞的严格控制，基质细胞产生干细胞因子（SCF）等正向调节剂和转化生长因子-β（TGF-β）等负向调节剂。基质细胞如何通过正向和负向调节之间的平衡来实现或维持这种平衡尚不清楚。我们通过静脉注射 5-氟尿嘧啶（5-FU）和脂多糖（LPS）到 C3H/HeN 小鼠中，以破坏肥大细胞的发育，从而揭示肥大细胞调节的机制。5-FU 处理会导致 BM 和脾脏中的肥大细胞祖细胞（集落形成单位（CFU）-mast）数量迅速减少，随后 CFU-mast 数量迅速恢复。在 BM 和脾脏中，SCF 基因的表达水平在稳态时只有 TGF-β的 1/50。在 5-FU 处理后，BM 中的 SCF mRNA 水平明显增加，接近 TGF-β mRNA 水平，而脾脏中的 SCF 水平则表现出有限的波动，其增加与 TGF-β水平的增加平行。相比之下，LPS 处理会导致 BM 中的 CFU-mast 数量迅速减少，而脾脏中的 CFU-mast 数量迅速增加。在 LPS 处理后，BM 中的 SCF mRNA 水平明显下降，而脾脏中的 SCF 水平保持不变。这些结果表明，在稳态下，BM 和脾脏中的肥大细胞发育受到负信号的主导，而在 5-FU 和 LPS 等生物应激条件下，BM 中的正和负调节之间的平衡可以改变，但在脾脏中则不能。BM 和脾脏中肥大细胞发育的调节差异可能反映了组织特异性基质细胞的不同作用。
