CD34 facilitates the development of allergic asthma
CD34 facilitates the development of allergic asthma
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DOI：
10.1182/blood-2006-12-062448
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发表时间：
2007-09-15
期刊：
影响因子：
20.3
通讯作者：
McNagny, Kelly M.
中科院分区：
文献类型：
--
作者：
Blanchet, Marie-Rene;Maltby, Steven;McNagny, Kelly M.
哮喘是一种依赖于嗜酸性粒细胞和肥大细胞渗入肺内的肺部炎症性疾病。CD34是这两种细胞都表达的唾液粘蛋白，我们使用CD34(-/-)小鼠和标准的哮喘小鼠模型来评估CD34表达在疾病发展中的重要性。与野生型(Wt)小鼠相比，CD34(-/-)小鼠的过敏性哮喘的所有特征都显著减少，包括呼吸道炎症细胞浸润减少、气道高反应性和肥大细胞招募。骨髓移植实验证实，这些缺陷是由于骨髓来源的细胞表达CD34所致。然而，这并不是由于不能对抗原做出反应，因为在每个细胞的基础上，wt和CD34(-/-)炎性细胞在细胞因子产生方面表现出相同的反应。我们发现CD34(-/-)嗜酸性粒细胞的流动性在体外显著降低，这与CD34作为细胞-细胞黏附抑制因子的模型是一致的。综上所述，我们的数据表明CD34增强了肥大细胞和嗜酸性粒细胞的侵袭性，这些细胞表达CD34是过敏性哮喘发生的先决条件。
Asthma is a pulmonary inflammatory disease dependent on eosinophil and mast cell infiltration into the lung. CD34 is a sialomucin expressed by both of these cell types, and we have used CD34(-/-) mice and a standard mouse model of asthma to evaluate the importance of CD34 expression on disease development. In comparison with wild-type (wt) mice, CD34(-/-) mice exhibited a dramatic reduction in all hallmarks of allergic asthma, including lowered airway inflammatory cell infiltration, airway hyperresponsiveness, and mast-cell recruitment. Bone marrow transplantation experiments confirmed that these defects are due to CD34 expression by bone marrow-derived cells. This was not, however, due to an inability to respond to antigen as, on a per cell basis, wt and CD34(-/-) inflammatory cells exhibit identical responses in cytokine production. We found a striking reduction in mobility of CD34(-/-) eosinophils in vitro, the major component of inflammatory infiltrates, which was consistent with proposed models for CD34 as an inhibitor of cell-cell adhesion. In summary, our data suggest that CD34 enhances mast-cell and eosinophil invasiveness and that its expression by these cells is a prerequisite for development of allergic asthma.