Grabbe J, Welker P, Dippel E, Czarnetzki B M
Department of Dermatology, University Clinics Rudolf Virchow, Free University, Berlin, Germany.
Arch Dermatol Res. 1994;287(1):78-84. doi: 10.1007/BF00370723.
Mechanisms affecting mast cell and melanocyte growth and function are still poorly understood. This report summarizes the current state of knowledge on a recently described growth factor for both these cell types and for primitive haematopoietic stem cells. Stem cell factor (SCF), also named mast cell growth factor or kit-ligand, has only recently been cloned and has been shown to be encoded on human chromosome 12. It may be of specific importance in cutaneous physiology and pathology since it is produced by several cell types in the skin (e.g. fibroblasts, keratinocytes, endothelial cells) and since it affects melanocyte and mast cell growth, survival, secretion and adhesion as well as migration into tissues. Defects in the genes encoding for the SCF receptor (c-kit-protein) have been shown to be responsible for human piebaldism. A pathogenetic role in mastocytosis has recently been proposed, but remains to be proven. SCF receptor expression is decreased on cells of some malignant cell lines compared to their physiological counterparts, making it unlikely that SCF is a key factor in malignant transformation and cellular hyperproliferation. In haematopoiesis, SCF acts primarily in concert with other growth factors, and we show here that alone in serum-free culture it has no effect on mast cell growth. Furthermore, there is evidence that besides SCF, additional mast cell growth factors are secreted by fibroblasts and keratinocytes, suggesting a complex orchestration of several growth factors in the regulation of cutaneous growth and differentiation in which SCF plays only one part.
影响肥大细胞和黑素细胞生长及功能的机制仍未完全明了。本报告总结了目前关于一种最近描述的、对这两种细胞类型以及原始造血干细胞均有作用的生长因子的知识现状。干细胞因子(SCF),也被称为肥大细胞生长因子或kit配体,直到最近才被克隆出来,并且已证明它由人类12号染色体编码。它在皮肤生理和病理过程中可能具有特殊重要性,因为它由皮肤中的几种细胞类型(如成纤维细胞、角质形成细胞、内皮细胞)产生,而且它会影响黑素细胞和肥大细胞的生长、存活、分泌、黏附以及向组织内的迁移。已证明编码SCF受体(c-kit蛋白)的基因缺陷是导致人类斑驳病的原因。最近有人提出它在肥大细胞增多症中具有致病作用,但仍有待证实。与它们的生理对应细胞相比,某些恶性细胞系的细胞上SCF受体表达降低,这使得SCF不太可能是恶性转化和细胞过度增殖的关键因素。在造血过程中,SCF主要与其他生长因子协同起作用,并且我们在此表明,在无血清培养中单独使用时它对肥大细胞生长没有影响。此外,有证据表明除了SCF之外,成纤维细胞和角质形成细胞还分泌其他肥大细胞生长因子,这表明在皮肤生长和分化的调节过程中,几种生长因子存在复杂的协同作用,而SCF仅起其中一部分作用。