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Effects of glucocorticoid and cysteinyl leukotriene 1 receptor antagonist on CD34 + hematopoietic cells in bone marrow of asthmatic mice

摘要Background Corticosteroids remain the most effective therapy available for asthma. They have widespread effects on asthmatic airway inflammation. However, little is known about the effects of corticosteroids on the production of bone marrow inflammatory cells in asthma. This study observed the effects of glucocorticoid and cysteinyl leukotriene 1 receptor antagonist on CD34 + hematopoietic cells, so as to explore the possible effectiveness of a bone marrow-targeted anti-inflammatory strategy.Methods Balb/c mice were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. For two consecutive weeks, asthmatic mice were challenged with OVA while being given either prednisone, montelukast, prednisone plus montelukast, or sterile saline solution. The mice were killed 24 hours after the last challenge with OVA, and bronchoalveolar lavage fluid (BALF),peripheral blood, and bone marrow were collected. Eosinophils in peripheral blood and BALF, and nucleated cells in BALF, peripheral blood, and bone marrow were counted. The percentages of CD34+cells, CD4 + T lymphocytes and CD8 + T lymphocytes among nucleated cells in peripheral blood and bone marrow were counted by flow cytometry. Immunocytochemistry and in situ hybridization were employed to detect expression of CD34 and interleukin (IL)-5Rαx mRNA (CD34 + IL-5Rα mRNA+ cells)among bone marrow hematopoietic cells.Results Compared with the sterile saline solution group, the number of eosinophils in BALF and peripheral blood, CD34 + cells in peripheral blood and bone marrow, and CD34 + IL-5Rc mRNA+ cells in bone marrow of mice from the prednisone and prednisone plus montelukast groups were significantly lower (P<0.01). The number of eosinophils in BALF from the montelukast group was also significantly lower (P<0.05).Conclusions The results suggest that, in this asthmatic mouse model, prednisone probably inhibits proliferation, differentiation, and migration of CD34 + cells in bone marrow, blocks eosinophilopoiesis in bone marrow, and interferes with eosinophil migration into peripheral blood and subsequent recruitment in the airway. In addition, montelukast may suppress eosinophil infiltration into the lungs of asthmatic mice. However, a significant inhibitory effect of montelukast on the proliferation and miqration of CD34+ cells and a cooperating effect with prednisone on bone marrow of asthmatic mice were not observed.

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作者 毛辉 [1] 殷凯生 [1] 王曾礼 [2] 李富宇 [3] 张希龙 [1] 刘春涛 [2] 雷松 [4] 学术成果认领
作者单位 Department of Respiratory Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China [1] Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China [2] Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China [3] Department of Tumor Biological Therapy, West China Hospital, Sichuan University, Chengdu 610041, China [4]
分类号 R5
栏目名称 ORIGINAL ARTICLES
发布时间 2004-06-18
基金项目
国家自然科学基金
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中华医学杂志(英文版)

中华医学杂志(英文版)

2004年117卷4期

592-597页

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