Division of Allergy and Clinical Immunology, Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
J Immunol. 2010 Feb 1;184(3):1463-74. doi: 10.4049/jimmunol.0901865. Epub 2009 Dec 30.
Expression of Fc epsilonRI on basophils and mast cells is modulated by IgE Ab. Previous studies have noted in vivo receptor expression dynamics that are discordant with expectations derived from in vitro studies. The current study presents a formal hypothesis to explain the discordant observations and tests two assumptions that underlie a proposed model of receptor dynamics. After first showing that a murine model of receptor expression on basophils recapitulates observations made using human basophils, the effect of changes in IgE on basophil egress rates was examined. In the proposed model, egress rates from bone marrow (BM) were assumed to be unaffected by changes in IgE concentration. Egress was tested by examining the labeling of BM and peripheral blood (BL) basophils at various times after injection of BrdU with and without injection with IgE. The IgE Ab did not alter the appearance of BrdU label in peripheral BL basophils. In addition, BM and BL basophils were responsive to the elevations in IgE, with receptor expression increasing on BM basophils before BL basophils. It was also noted that BL basophils expressed approximately 50% of the receptor density of BM basophils. There was a 3-fold greater synthetic rate of Fc epsilonRI on BM basophils that readily explained the difference. These results provide support for the proposed hypothesis of rapid changes in receptor expression being controlled by cell replacement. The studies also support a model whereby receptor expression is limited by cell division and that basophils, once mature, slow their rate of receptor synthesis.
Fc epsilonRI 在嗜碱性粒细胞和肥大细胞上的表达受 IgE Ab 调节。先前的研究注意到体内受体表达动力学与体外研究得出的预期不一致。本研究提出了一个正式的假设来解释这些不一致的观察结果,并检验了一个受体动力学模型所基于的两个假设。首先,我们展示了一种在嗜碱性粒细胞上表达受体的小鼠模型,该模型重现了使用人嗜碱性粒细胞所做的观察结果,然后研究了 IgE 变化对嗜碱性粒细胞迁出率的影响。在提出的模型中,假设骨髓(BM)中迁出率不受 IgE 浓度变化的影响。通过检查注射 BrdU 后不同时间 BM 和外周血(BL)嗜碱性粒细胞的标记,测试了迁出。IgE Ab 不会改变外周 BL 嗜碱性粒细胞中 BrdU 标记的外观。此外,BM 和 BL 嗜碱性粒细胞对 IgE 的升高有反应,BM 嗜碱性粒细胞上的受体表达在 BL 嗜碱性粒细胞之前增加。还注意到,BL 嗜碱性粒细胞表达的受体密度约为 BM 嗜碱性粒细胞的 50%。BM 嗜碱性粒细胞上的 Fc epsilonRI 合成率增加了 3 倍,这很好地解释了这种差异。这些结果为快速改变受体表达受细胞替代控制的假设提供了支持。这些研究还支持了这样一种模型,即受体表达受细胞分裂限制,并且一旦成熟,嗜碱性粒细胞就会降低其受体合成的速度。