Airway responsiveness in CD38-deficient mice in allergic airway disease: studies with bone marrow chimeras
Airway responsiveness in CD38-deficient mice in allergic airway disease: studies with bone marrow chimeras
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DOI：
10.1152/ajplung.00227.2014
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发表时间：
2015-03-01
影响因子：
4.9
通讯作者：
Kannan, Mathur S.
中科院分区：
文献类型：
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作者：
Guedes, Alonso G. P.;Jude, Joseph A.;Kannan, Mathur S.
CD 38是一种细胞表面蛋白，参与气道平滑肌的钙信号传导和收缩。它在正常气道反应性和气道暴露于IL-13和TNF-α后发展的气道高反应性（AHR）中起作用，但似乎对响应于细胞因子的气道炎症不是关键的。CD 38还参与T细胞介导的对蛋白质抗原的免疫应答。在这项研究中，我们评估了CD 38对AHR和炎症的贡献，两种不同的过敏原，卵清蛋白和流行病学相关的环境真菌链格孢菌。我们还产生了骨髓嵌合体，以评估卵清蛋白攻击后，CD 38（+/+）炎性细胞是否会恢复CD 38缺陷（CD 38（-/-））宿主中的AHR。结果表明，野生型（WT）小鼠比Cd 38（-/-）小鼠在用任一变应原激发后对吸入乙酰甲胆碱产生更大的AHR，具有相当的气道炎症。相互骨髓移植没有改变WT和Cd 38（-/-）小鼠之间的天然气道表型差异，表明Cd 38（-/-）小鼠的较低气道反应性源于Cd 38（-/-）肺实质细胞。在从任一来源和卵清蛋白激发的骨髓转移后，Cd 38（-/-）宿主的表型被部分逆转，而WT宿主的气道表型被保留。气道炎症在Cd 38（-/-）和WT嵌合体中相似。这些结果表明，造血细胞上CD 38的丢失不足以预防AHR，并且气道炎症的程度不是小鼠中AHR的主要潜在决定因素。
CD38 is a cell-surface protein involved in calcium signaling and contractility of airway smooth muscle. It has a role in normal airway responsiveness and in airway hyperresponsiveness (AHR) developed following airway exposure to IL-13 and TNF-alpha but appears not to be critical to airway inflammation in response to the cytokines. CD38 is also involved in T cell-mediated immune response to protein antigens. In this study, we assessed the contribution of CD38 to AHR and inflammation to two distinct allergens, ovalbumin and the epidemiologically relevant environmental fungus Alternaria. We also generated bone marrow chimeras to assess whether Cd38(+/+) inflammatory cells would restore AHR in the CD38-deficient (Cd38(-/-)) hosts following ovalbumin challenge. Results show that wild-type (WT) mice develop greater AHR to inhaled methacholine than Cd38(-/-) mice following challenge with either allergen, with comparable airway inflammation. Reciprocal bone marrow transfers did not change the native airway phenotypic differences between WT and Cd38(-/-) mice, indicating that the lower airway reactivity of Cd38(-/-) mice stems from Cd38(-/-) lung parenchymal cells. Following bone marrow transfer from either source and ovalbumin challenge, the phenotype of Cd38(-/-) hosts was partially reversed, whereas the airway phenotype of the WT hosts was preserved. Airway inflammation was similar in Cd38(-/-) and WT chimeras. These results indicate that loss of CD38 on hematopoietic cells is not sufficient to prevent AHR and that the magnitude of airway inflammation is not the predominant underlying determinant of AHR in mice.