Institute of Zoonosis, College of Animal Sciences and Veterinary Medicine, Jilin University, Changchun, China.
Am J Pathol. 2011 Sep;179(3):1199-210. doi: 10.1016/j.ajpath.2011.05.022. Epub 2011 Jul 8.
The presence of eosinophils in the lung is often regarded as a defining feature of asthma. On allergen stimulation, numbers of eosinophils and their progenitors are increased in both the bone marrow and lungs. Eosinophil progenitors provide an ongoing supply of mature eosinophils. Here, we report that deficiency in the regulator of calcineurin 1 gene (Rcan1) leads to a near-complete absence of eosinophilia in ovalbumin-induced allergic asthma in mice. In the absence of Rcan1, bone marrow cells produce significantly fewer eosinophils in vivo and in vitro on interleukin-5 stimulation. Importantly, eosinophil progenitor populations are significantly reduced in both naïve and ovalbumin-challenged Rcan1(-/-) mice. Bone marrow cells from Rcan1(-/-) mice are capable of developing into fully mature eosinophils, suggesting that Rcan1 is required for eosinophil progenitor production but may not be necessary for eosinophil maturation. Thus, Rcan1 represents a novel contributor in the development of eosinophilia in allergic asthma through regulation of eosinophil progenitor production.
肺组织中嗜酸性粒细胞的存在通常被认为是哮喘的一个特征。在过敏原刺激下，骨髓和肺部的嗜酸性粒细胞及其前体细胞数量增加。嗜酸性粒细胞前体细胞为成熟的嗜酸性粒细胞提供持续的供应。在这里，我们报告钙调神经磷酸酶调节因子 1 基因（Rcan1）缺陷导致卵清蛋白诱导的过敏性哮喘小鼠几乎完全没有嗜酸性粒细胞增多。在缺乏 Rcan1 的情况下，骨髓细胞在体内和体外白细胞介素-5 刺激下产生的嗜酸性粒细胞明显减少。重要的是，在未受挑战和卵清蛋白挑战的 Rcan1(-/-)小鼠中，嗜酸性粒细胞前体细胞群明显减少。Rcan1(-/-)小鼠的骨髓细胞能够完全发育为成熟的嗜酸性粒细胞，这表明 Rcan1 是嗜酸性粒细胞前体细胞产生所必需的，但可能不是嗜酸性粒细胞成熟所必需的。因此，Rcan1 通过调节嗜酸性粒细胞前体细胞的产生，成为过敏性哮喘嗜酸性粒细胞增多症发展的一个新的贡献者。
