Mahmoud A A, Stone M K, Kellermeyer R W
J Clin Invest. 1977 Sep;60(3):675-82. doi: 10.1172/JCI108819.
In earlier studies, methods were developed to raise specific antibodies in rabbits against purified suspensions of mouse or human eosinophils. On administration of antieosinophil serum (AES) to mice, the mature eosinophils in tissues, peripheral blood, and bone marrow were depleted, while the immature eosinophil pool in the bone marrow was observed to proliferate. The current investigations explore the generation of eosinophilopoietic factors during AES-induced eosinophilopenia. Mice received three injections of AES, one every other day. As the peripheral eosinophil counts started to recover after the last AES injection, the serum was collected and transferred to normal animals. Within 2 days the recipients showed an increase in peripheral blood as well as in bone marrow eosinophils. The rise in bone marrow eosinophils was due to newly formed cells as evidenced by increased uptake of [(3)H]thymidine. The generation of eosinophilopoietic activity was specifically related to depletion of eosinophils but not neutrophils. The eosinophilopoietic activity was: (a) dependent on the volume of serum transferred, (b) lost on dialysis, and (c) largely heat labile. The activity eluted as a low molecular weight substance on G-25 Sephadex and was digested by pronase but not by trypsin. Active fractions collected from G-25 columns were not chemotactic for the eosinophils in vitro. Thus, specific depletion of mature eosinophils generates a low molecular weight peptide which stimulates eosinophilopoiesis in vivo. It is suggested that this substance be named eosinophilopoietin.
在早期研究中,已开发出在兔体内产生针对纯化的小鼠或人嗜酸性粒细胞悬液的特异性抗体的方法。给小鼠注射抗嗜酸性粒细胞血清(AES)后,组织、外周血和骨髓中的成熟嗜酸性粒细胞减少,而骨髓中未成熟嗜酸性粒细胞池则增殖。当前的研究探索了AES诱导嗜酸性粒细胞减少期间嗜酸性粒细胞生成因子的产生。小鼠每隔一天接受三次AES注射。在最后一次AES注射后,随着外周嗜酸性粒细胞计数开始恢复,收集血清并转移至正常动物体内。在2天内,受体动物的外周血和骨髓嗜酸性粒细胞均增加。骨髓嗜酸性粒细胞的增加是由于新形成的细胞,这通过[(3)H]胸腺嘧啶核苷摄取增加得到证明。嗜酸性粒细胞生成活性的产生与嗜酸性粒细胞而非中性粒细胞的减少特异性相关。嗜酸性粒细胞生成活性:(a)取决于转移的血清量,(b)透析后丧失,(c)很大程度上对热不稳定。该活性在G - 25葡聚糖凝胶上以低分子量物质洗脱,并被链霉蛋白酶消化,但不被胰蛋白酶消化。从G - 25柱收集的活性级分在体外对嗜酸性粒细胞无趋化作用。因此,成熟嗜酸性粒细胞的特异性减少产生一种低分子量肽,其在体内刺激嗜酸性粒细胞生成。建议将该物质命名为嗜酸性粒细胞生成素。