Kasugai T, Okada M, Morimoto M, Arizono N, Maeyama K, Yamada M, Tei H, Dohmae K, Onoue H, Newlands G F
Department of Pathology, Medical School, Osaka University, Japan.
Blood. 1993 May 15;81(10):2521-9.
All basophils, mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC) are derived from the multipotential hematopoietic stem cell. Mutations at the c-kit locus resulted in deficiency of MMC and CTMC in both mice and rats. To investigate the role of the c-kit receptor tyrosine kinase for production of basophils, we used white spotting/white spotting (Ws/Ws) mutant rats that have a small deletion at the tyrosine kinase domain of the c-kit gene. When Ws/Ws, nude athymic, and normal (+/+) rats were infected with Nippostrongylus brasiliensis (NB), the number of basophils increased greater than 50-fold in the peripheral blood of Ws/Ws and +/+ rats but did not increase in that of nude rats. Blood histamine concentration increased significantly in Ws/Ws and +/+ rats but did not increase in nude rats. Immature basophils increased greater than 10-fold in the bone marrow of Ws/Ws and +/+ rats but did not increase in that of nude rats. Mature and immature basophils that developed after the NB infection were identified by electron microscopy. The present result confirms that T-cell-derived cytokines are indispensable for the augmented production of basophils and suggests that stimulation via the c-kit receptor may not be necessary for the augmented production.
所有嗜碱性粒细胞、黏膜型肥大细胞(MMC)和结缔组织型肥大细胞(CTMC)均源自多能造血干细胞。c-kit基因座的突变导致小鼠和大鼠体内MMC和CTMC缺乏。为了研究c-kit受体酪氨酸激酶在嗜碱性粒细胞生成中的作用,我们使用了白色斑点/白色斑点(Ws/Ws)突变大鼠,其c-kit基因的酪氨酸激酶结构域存在小片段缺失。当Ws/Ws大鼠、无胸腺裸鼠和正常(+/+)大鼠感染巴西日圆线虫(NB)时,Ws/Ws大鼠和+/+大鼠外周血中的嗜碱性粒细胞数量增加了50倍以上,而裸鼠外周血中的嗜碱性粒细胞数量未增加。Ws/Ws大鼠和+/+大鼠血液中的组胺浓度显著升高,而裸鼠血液中的组胺浓度未升高。Ws/Ws大鼠和+/+大鼠骨髓中的未成熟嗜碱性粒细胞数量增加了10倍以上,而裸鼠骨髓中的未成熟嗜碱性粒细胞数量未增加。通过电子显微镜鉴定了NB感染后发育的成熟和未成熟嗜碱性粒细胞。目前的结果证实,T细胞衍生的细胞因子对于嗜碱性粒细胞的增加生成是不可或缺的,并表明通过c-kit受体的刺激对于增加生成可能不是必需的。