Leftwich J A, Westin E H, Huff T F
Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond 23298.
J Immunol. 1992 May 1;148(9):2894-8.
Mast cell committed progenitors are nongranulated cells found in mesenteric lymph nodes of mice infected with Nippostrongylus brasiliensis (Nb-MLN) but not from normal mice. Mast cell committed progenitors can respond to either IL-3 or to a factor(s) present in 3T3 fibroblast conditioned media (F-CM) by formation of mast cell colonies. Previous studies from ours and other laboratories suggested that mast cell differentiation involved the W allele product, c-kit, as a receptor and Sl allele product, stem cell factor, as a growth factor. We report here that Nb-MLN cells, which can respond to F-CM by mast cell colony formation, also contain cells that express message for c-kit, and that c-kit message cannot be detected in naive mesenteric lymph node cells, which cannot respond to F-CM. Antisense oligonucleotides to c-kit inhibit mast cell colony formation by Nb-MLN cells in response to F-CM, but not to conditioned medium of PWM-stimulated spleen cells as a source of IL-3. The antisense oligonucleotides also inhibit the degree of granulation by mast cells derived from culture. The results suggest that c-kit and its ligand, stem cell factor, are necessary for mast cell-committed progenitors to proliferate and granulate in response to F-CM but not IL-3.
肥大细胞定向祖细胞是在感染巴西日圆线虫的小鼠肠系膜淋巴结(Nb-MLN)中发现的无颗粒细胞,而正常小鼠中则没有。肥大细胞定向祖细胞可通过形成肥大细胞集落对IL-3或3T3成纤维细胞条件培养基(F-CM)中存在的一种或多种因子作出反应。我们实验室和其他实验室之前的研究表明,肥大细胞分化涉及W等位基因产物c-kit作为受体以及Sl等位基因产物干细胞因子作为生长因子。我们在此报告,能够通过肥大细胞集落形成对F-CM作出反应的Nb-MLN细胞也包含表达c-kit信使的细胞,而在不能对F-CM作出反应的幼稚肠系膜淋巴结细胞中检测不到c-kit信使。针对c-kit的反义寡核苷酸可抑制Nb-MLN细胞对F-CM作出反应而形成肥大细胞集落,但不能抑制作为IL-3来源的PWM刺激的脾细胞条件培养基所诱导的肥大细胞集落形成。反义寡核苷酸还可抑制培养来源的肥大细胞的颗粒化程度。结果表明,c-kit及其配体干细胞因子对于肥大细胞定向祖细胞响应F-CM而非IL-3进行增殖和颗粒化是必需的。