Effects of glucocorticoid and cysteinyl leukotriene 1 receptor antagonist on CD_(34)~+ hematopoietic

来源 :Chinese Medical Journal | 被引量 : 0次 | 上传用户:stat2009
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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 CD 34 + 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 CD 34 + cells, CD 4 + T lymphocytes and CD 8 + 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 CD 34 and interleukin (IL)-5Rα mRNA (CD 34 + 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, CD 34 + cells in peripheral blood and bone marrow, and CD 34 + IL-5Rα 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 CD 34 + 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 migration of CD 34 + cells and a cooperating effect with prednisone on bone marrow of asthmatic mice were not observed. Background Corticosteroids remain the most effective therapy available for asthma. 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 CD 34 + 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, the 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) , and bone marrow were collected. Eosinophils in peripheral blood and BALF, and nucleated cel ls in BALF, peripheral blood, and bone marrow were counted. The percentages of CD 34 + cells, CD 4 + T lymphocytes and CD 8 + 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) -5Rα 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, CD 34 + cells in peripheral blood and bone marrow, and CD 34 + IL-5Rα 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 migr ation of CD 34 + cells in bone marrow, blocks eosinophilopoiesis in bone marrow, and interferes with eosinophil migration into peripheral blood and subsequent recruitment in the airway. However, montelukast may suppress eosinophil infiltration into the lungs of asthmatic mice. However, a significant inhibitory effect of montelukast on the proliferation and migration of CD 34 + cells and a cooperating effect with prednisone on bone marrow of asthmatic mice were not observed.
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