Galli S J, Tsai M, Wershil B K
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts.
Am J Pathol. 1993 Apr;142(4):965-74.
Many years ago, alert observers noticed among thousands of laboratory mice a few individuals that, unlike their littermates, exhibited areas of white spotting on their fur. No one could have predicted then that an effort to understand the basis for these abnormalities would ultimately contribute to the characterization of a receptor (c-kit) and a corresponding ligand (stem cell factor, SCF) that are critical not only to the migration and development of melanocytes, but also to hematopoiesis, gametogenesis, mast cell development, and, perhaps, development of the central nervous system. Nor could anyone have foretold then that this receptor and ligand would be shown to regulate the development of multiple distinct cellular lineages not only in mice, but also in humans and other primates, or that c-kit and its ligand would be found to influence the secretory function of cells bearing this receptor, as well as their development. Investigation of the effects of SCF on a single cell type, the mast cell, has produced the most complete picture of the spectrum of biological processes that can be regulated by interactions between c-kit and its ligand. This work shows that SCF critically regulates the migration and survival of mast cell precursors, promotes the proliferation of both immature and mature mast cells, enhances mast cell maturation, directly induces secretion of mast cell mediators, and can regulate the extent of mediator release in mast cells activated by IgE-dependent mechanisms. Indeed, SCF may well prove to be one of the most important of the factors influencing mast cell numbers, phenotype, and function in both health and disease. It now seems virtually certain that further studies of c-kit and SCF will produce important new insights into problems as diverse as the regulation of lineage commitment during normal hematopoiesis or the development and function of the central nervous system. And even though an effect on mast cell development was one of the last phenotypic abnormalities to be recognized in mice with mutations affecting the genes encoding c-kit or SCF, mast cells will continue to represent an important model system for analyzing the biology of c-kit and its ligand.
许多年前，敏锐的观察者在数千只实验小鼠中注意到有几只小鼠与它们的同窝小鼠不同，其皮毛上有白色斑点区域。当时没有人能够预测到，对这些异常现象的基础进行研究最终会促成一种受体（c-kit）和一种相应配体（干细胞因子，SCF）的特性描述，它们不仅对黑素细胞的迁移和发育至关重要，而且对造血作用、配子发生、肥大细胞发育以及可能对中枢神经系统的发育也至关重要。当时也没有人能够预见到，这种受体和配体不仅在小鼠中，而且在人类和其他灵长类动物中会被证明可调节多种不同细胞谱系的发育，或者会发现c-kit及其配体不仅会影响表达该受体的细胞的发育，还会影响其分泌功能。对SCF对单一细胞类型肥大细胞的作用进行的研究，最为完整地展现了可由c-kit及其配体之间的相互作用所调节的生物过程谱。这项研究表明，SCF对肥大细胞前体的迁移和存活起着关键的调节作用，促进未成熟和成熟肥大细胞的增殖，增强肥大细胞的成熟，直接诱导肥大细胞介质的分泌，并可调节由IgE依赖性机制激活的肥大细胞中介质释放的程度。事实上，SCF很可能被证明是在健康和疾病状态下影响肥大细胞数量、表型和功能的最重要因素之一。现在几乎可以肯定的是，对c-kit和SCF的进一步研究将为诸如正常造血过程中谱系定向的调节或中枢神经系统的发育和功能等各种问题带来重要的新见解。尽管对肥大细胞发育的影响是在影响编码c-kit或SCF基因的突变小鼠中最后被认识到的表型异常之一，但肥大细胞仍将继续是分析c-kit及其配体生物学特性的重要模型系统。
