Johansson A-K, Sjöstrand M, Tomaki M, Samulesson A-M, Lötvall J
Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Internal Medicine, Göteborg University, Sweden.
Allergy. 2004 Oct;59(10):1080-6. doi: 10.1111/j.1398-9995.2004.00596.x.
The specific mechanisms that alter bone marrow (BM) eosinophilopoiesis in allergen-induced inflammation are poorly understood. The aims of this study were to evaluate (a) whether the number of BM CD34(+) cells is altered due to allergen sensitization and exposure in vivo and (b) whether BM CD34(+) cells produce and release interleukin (IL)-5, IL-3 and granulocyte macrophage-colony stimulating factor (GM-CSF) after stimulation in vitro. A mouse model of ovalbumin (OVA)-induced airway inflammation was used. Bone marrow CD34(+) cells were cultured in vitro and the cytokine release was measured by enzyme-linked immunosorbent assay. The IL-5-production from CD34(+) cells was confirmed by immunocytochemistry. Airway allergen exposure increased the number of BM CD34(+) cells (P = 0.01). Bone marrow CD34(+) cells produced IL-5 when stimulated with the allergen OVA in vitro, but not IL-3 or GM-CSF. Nonspecific stimulus with calcium ionophore and phorbol-myristate-acetate of BM CD34(+) cells caused release of IL-5, IL-3 and GM-CSF. The induced release of IL-5 was increased in alum-injected vs naive mice (P = 0.02), but was not affected by allergen sensitization and exposure. The release of IL-3 and GM-CSF was increased after allergen sensitization and exposure (P < 0.02). In conclusion, allergen can stimulate BM CD34(+) cells to produce IL-5 protein. It is likely that the CD34(+) cells have autocrine functions and thereby regulate the early stages of BM eosinophilopoiesis induced by airway allergen exposure. Alum, a commonly used adjuvant, enhances the release of IL-5 and may thereby enhance eosinophilopoiesis.
变应原诱导的炎症中改变骨髓嗜酸性粒细胞生成的具体机制尚不清楚。本研究的目的是评估:(a)体内变应原致敏和暴露是否会改变骨髓CD34(+)细胞的数量;(b)体外刺激后骨髓CD34(+)细胞是否产生并释放白细胞介素(IL)-5、IL-3和粒细胞巨噬细胞集落刺激因子(GM-CSF)。采用卵清蛋白(OVA)诱导气道炎症的小鼠模型。体外培养骨髓CD34(+)细胞,并用酶联免疫吸附测定法测量细胞因子释放。通过免疫细胞化学证实CD34(+)细胞产生IL-5。气道变应原暴露增加了骨髓CD34(+)细胞的数量(P = 0.01)。体外用变应原OVA刺激时,骨髓CD34(+)细胞产生IL-5,但不产生IL-3或GM-CSF。用钙离子载体和佛波醇肉豆蔻酸酯乙酸盐对骨髓CD34(+)细胞进行非特异性刺激会导致IL-5、IL-3和GM-CSF的释放。与未处理小鼠相比,注射明矾的小鼠中IL-5的诱导释放增加(P = 0.02),但不受变应原致敏和暴露的影响。变应原致敏和暴露后IL-3和GM-CSF的释放增加(P < 0.02)。总之,变应原可刺激骨髓CD34(+)细胞产生IL-5蛋白。CD34(+)细胞可能具有自分泌功能,从而调节气道变应原暴露诱导的骨髓嗜酸性粒细胞生成的早期阶段。常用佐剂明矾可增强IL-5的释放,从而可能增强嗜酸性粒细胞生成。