Dorman Sandra C, Sehmi Roma, Gauvreau Gail M, Watson Rick M, Foley Ronan, Jones Graham L, Denburg Judah A, Inman Mark D, O'Byrne Paul M
Asthma Research Group, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Am J Respir Crit Care Med. 2004 Mar 1;169(5):565-72. doi: 10.1164/rccm.200307-1024OC. Epub 2003 Dec 4.
Allergen inhalation is associated with increased eosinophil/basophil progenitors in bone marrow 24 hours after allergen inhalation. This study examined the kinetics of eosinophilopoiesis in dual (n = 14), compared with isolated early, responders (n = 12). Dual responders, in contrast to isolated early responders, develop significant sputum and blood eosinophilia and prolonged airway hyperresponsiveness. Bone marrow aspirates were taken before and 5, 12, 24, and 48 hours after allergen inhalation. In dual responders, increases in interleukin (IL)-3-responsive progenitors were detected as early as 5 hours after allergen inhalation, and IL-5-responsive progenitors were detected at 12 and 24 hours. No changes were detected in isolated early responders. Bone marrow IL-5 protein levels increased at 12 and 24 hours in dual responders only and these increases correlated with increases in IL-5-responsive progenitors. In addition, bone marrow IFN-gamma levels increased in dual responders at 48 hours. These data demonstrate that, in dual responders, there is allergen-induced activation of an eosinophilopoietic process that is rapid and sustained, and a relationship between increased bone marrow IL-5 levels and increased eosinophil production. We propose that after allergen inhalation, time-dependent changes in cytokine levels in the bone marrow control differentiation of eosinophil/basophil progenitors.
变应原吸入与变应原吸入后24小时骨髓中嗜酸性粒细胞/嗜碱性粒细胞祖细胞增加有关。本研究比较了双相反应者（n = 14）与孤立的早期反应者（n = 12）中嗜酸性粒细胞生成的动力学。与孤立的早期反应者相比，双相反应者会出现显著的痰液和血液嗜酸性粒细胞增多以及气道高反应性延长。在变应原吸入前以及吸入后5、12、24和48小时采集骨髓抽吸物。在双相反应者中，早在变应原吸入后5小时就检测到白细胞介素（IL）-3反应性祖细胞增加，在12和24小时检测到IL-5反应性祖细胞增加。在孤立的早期反应者中未检测到变化。仅在双相反应者中，骨髓IL-5蛋白水平在12和24小时升高，且这些升高与IL-5反应性祖细胞的增加相关。此外，双相反应者在48小时时骨髓干扰素-γ水平升高。这些数据表明，在双相反应者中，存在变应原诱导的快速且持续的嗜酸性粒细胞生成过程激活，以及骨髓IL-5水平升高与嗜酸性粒细胞生成增加之间的关系。我们提出，变应原吸入后，骨髓中细胞因子水平的时间依赖性变化控制着嗜酸性粒细胞/嗜碱性粒细胞祖细胞的分化。
