MOLECULAR BIOLOGY OF MAST CELL GROWTH AND DIFFERENTIATION

肥大细胞生长的调节和 差异取决于特定的连续可用性 生长因子及其相应受体的表达。 在促进肥大细胞生长的各种细胞因子中， 最重要的是干细胞因子（SCF）， 由基质细胞组成。我们已经报道过， 局部类固醇给药后在组织中观察到的细胞 是由于类固醇对SCF产生的影响。然后我们 探讨肥大细胞是否会因 通过Fas抗原（CD 95，APO-1）激活，从而提供了一种 可能有助于调节的因子独立途径 肥大细胞的数量。小鼠细胞系C57被发现可以快速地 Fas抗原聚集后发生凋亡。初级 小鼠骨髓来源的肥大细胞相对抵抗 抗Fas抗体。肥大细胞仅表达胞质FasL， 无法杀死表达FasL的靶细胞。为了确认 抑制人肥大细胞生长的细胞因子， 重组人干细胞因子依赖性人 骨髓来源的肥大细胞（HBMCs）， 干扰素γ（IFN-γ）-1b。在这些培养物中， 数量大幅下降。rhSCF plus的FACS分析 IFN-γ-1b处理的成熟HBMCs显示c-kit增加 和FcERI表达。肥大细胞的释放性没有增加。 因此，IFN-γ-1b能够抑制肥大细胞的生长， CD 34+细胞，这表明这种药物应被视为一种治疗癌症的药物。 用于治疗肥大细胞疾病的候选细胞因子 增殖肥大细胞的效应功能在两个 IgE依赖性和免疫复合物诱导的炎症在 部分由肥大细胞与结缔组织的相互作用决定 包括层粘连蛋白的组织基质成分。这影响了桅杆 细胞趋化性、组织定位和生物反应性。在 合作，我们发现SAA（血清淀粉样蛋白A）结合 诱导肥大细胞与结缔组织基质的粘附 这种基质和层粘连蛋白，帮助调节肥大细胞的募集， 血管外炎症部位。

The regulation of mast cell growth and differentiation depends upon the sequential availability of specific growth factors and the expression of their corresponding receptors. Among the various cytokines that promote mast cell growth, the most important is stem cell factor (SCF) which is produced in tissues by stromal cells. We have reported that the decrease in mast cells observed in tissues that follows topical steroid administration is due to the effect of the steroid on SCF production. We then explored whether mast cells undergo apoptosis in response to activation through Fas antigen (CD95, APO-1), thus providing a factor-independent pathway that could contribute to the regulation of mast cell number. The murine cell line, C57, was found to rapidly undergo apoptosis following aggregation of Fas antigen. Primary murine bone marrow derived mast cells were relatively resistant to anti-Fas antibody. Mast cells express cytoplasmic FasL only, and are unable to kill targets that express FasL. In an effect to identify cytokines that inhibit human mast cell growth, we cultured recombinant human stem cell factor (rhSCF)-dependent human bone marrow-derived mast cells (HBMCs) in the presence of interferon gamma (IFN-gamma)-1b. In these cultures HBMCs significantly decreased in number. FACS analysis of rhSCF plus IFN-gamma-1b-treated mature HBMCs revealed increased c-kit and FcERI expression. Mast cell releasibility was not increased. IFN-gamma-1b was thus able to suppress mast cell growth from CD34+ cells, suggesting that this agent should be considered as a candidate cytokine for the treatment of disorders of mast cell proliferation. The effector function of mast cells in both IgE-dependent and in immune complex-induced inflammation is in part determined by the interaction of mast cells with connective tissue matrix components including laminin. This influences mast cell chemotaxis, tissue location, and biologic responsiveness. In collaboration, we have found that SAA (serum amyloid A) bound to connective tissue matrix induces adhesion of mast cells to both this matrix and to laminin, helping to regulate mast cell recruitment at extravascular inflammatory sites.