糖皮质激素对卵蛋白致敏小鼠骨髓祖细胞扩增反应的干预

The intervention of glucocorticoid to expansion of bone marrow eosinophil progenitors to interleukin 5 in ovalbumin-induced mouse

目的探讨地塞米松对卵蛋白(OVA)诱导的小鼠骨髓细胞体外扩增的影响作用.方法以OVA及生理盐水致敏并激发BALB/c小鼠,建立各哮喘及对照组模型.分别于OVA激发后2、12、24、48和72h及生理盐水激发后24h处死小鼠,取支气管肺泡灌洗液(BALF)计数其中的白细胞和嗜酸性粒细胞(EOS)的数量.采用半固定培养骨髓细胞,培养基中分别加有白细胞介素5(1ng/ml)和不同浓度的地塞米松(0～ 0.2mg/ml),计数嗜酸性粒祖细胞克隆(Eo-CFU).结果 OVA激发2h以后BALF中白细胞总数和EOS显著高于对照组(P<0.05),过敏原激发24～48h小鼠骨髓Eo-CFU显著高于对照组(P<0.05).经低浓度的地塞米松(30.05 mg/ml)处理后的骨髓细胞Eo-CFU受到抑制(P<0.05)).结论过敏原诱导的气道嗜酸性粒细胞增多和骨髓中造血细胞性祖细胞的分化增殖增强有关,糖皮质激素对过敏原诱导的气道炎症的治疗作用可能部分通过其抑制骨髓造血功能实现的.

Objective To evaluate the effects of dexamethasone on allergen-induced changes in expansion of bone marrow eosinophil progenitors in ovalbumin (OVA)-sensitized mice.Methods BALB/c mice were sensitized and challenged by OVA to establish the asthmatic model.The control mice were sensitized and exposed to sterile saline.The sensitized mice were killed at 2,12,24,48,and 72h after challenged by OVA ;The control mice were killed at 24h after saline challenge.Eosinophils(EOS) and white blood cells(WBC) in bronchoalveolar lavage fluid(BALF) were counted.Bone marrow Eo-CFU were enumerated using a semisolid culture assay with 1ng/ml interleukin-5 and different concentration of dexamethasone(from 0 to 0.2mg/ml).Results We observed significant increases in BALF WBC,EOS by 2h after the OVA challenge (P<0.05).BM Eo-CFU were observed at 24h and persisted until at least 72h(P<0.05). Dexamethasone treatment(30.05 mg/ml) attenuated allergen-induced increases in bone marrow eosinophil progenitors(P<0.05).Conclusion Allergen-induced airway eosionophilia is accompanied by increases in bone marrow eosinophil progenitors,indicating expansion of the relevant stem-cell population. Glucocorticoid treatment attenuates allergen-induced airway inflammation is partly through suppression of bone marrow eosinophilopoiesis.