Galli S J, Iemura A, Garlick D S, Gamba-Vitalo C, Zsebo K M, Andrews R G
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02215.
J Clin Invest. 1993 Jan;91(1):148-52. doi: 10.1172/JCI116164.
Mast cell development in mice is critically regulated by stem cell factor (SCF), the term used here to designate a product of fibroblasts and other cell types that is a ligand for the tyrosine kinase receptor protein encoded by the proto-oncogene c-kit. However, the factors which regulate the size of mast cell populations in primates are poorly understood. Here we report that the subcutaneous administration of recombinant human SCF (rhSCF) to baboons (Papio cynocephalus) or cynomolgus monkeys (Macaca fascicularis) produced a striking expansion of mast cell populations in many anatomical sites, with numbers of mast cells in some organs of rhSCF-treated monkeys exceeding the corresponding values in control monkeys by more than 100-fold. Animals treated with rhSCF did not exhibit clinical evidence of mast cell activation, and discontinuation of treatment with rhSCF resulted in a rapid decline of mast cell numbers nearly to baseline levels. These findings are the first to demonstrate that a specific cytokine can regulate mast cell development in primates in vivo. They also provide the first evidence, in any mammalian species, to indicate that the cytokine-dependent expansion of tissue mast cell populations can be reversed when administration of the cytokine is discontinued.
小鼠体内肥大细胞的发育受到干细胞因子(SCF)的严格调控,本文中该术语用于指代成纤维细胞和其他细胞类型产生的一种产物,它是原癌基因c-kit编码的酪氨酸激酶受体蛋白的配体。然而,灵长类动物中调节肥大细胞群体大小的因素却知之甚少。在此我们报告,向狒狒(Papio cynocephalus)或食蟹猴(Macaca fascicularis)皮下注射重组人SCF(rhSCF),会使许多解剖部位的肥大细胞群体显著扩增,rhSCF处理的猴子某些器官中的肥大细胞数量比对照猴子的相应值高出100多倍。用rhSCF处理的动物未表现出肥大细胞激活的临床证据,停止rhSCF治疗会导致肥大细胞数量迅速下降至接近基线水平。这些发现首次证明特定细胞因子可在体内调节灵长类动物的肥大细胞发育。它们还在任何哺乳动物物种中首次提供证据表明,当停止细胞因子给药时,组织肥大细胞群体的细胞因子依赖性扩增可被逆转。