Department of Animal Science, Center of Excellence for Vaccine Research, University of Connecticut, Storrs, CT 06269,USA.
Cell Immunol. 2013 Feb;281(2):159-69. doi: 10.1016/j.cellimm.2013.03.001. Epub 2013 Mar 27.
The migration of eosinophils and lymphocytes into airways is a hallmark of allergic asthma; however, the role of broncho-alveolar macrophages (BAMs) in this inflammatory process has not been fully elucidated. Using a murine Ova model of allergic airway disease (AAD), RNA isolated from BAMs was used to assess differential gene expression via microarray and qRT-PCR. Significant increases in WBCs, eosinophilia, mucus accumulation and goblet cell hyperplasia were observed in Ova sensitized and challenged mice, which correlated with increased expression of genes associated with alternatively activated M2 macrophages (e.g. arginase 1, YM-1, YM-2, Resistin like-α, and EAR-11). Other genes associated with asthma including FcγRIIb, MMP-14, CCL-8, CCL-17, ADAM-8, LTBR1, aquaporin-9 and IL-7R were also expressed at higher levels in Ova sensitized/challenged animals when compared to BAMs isolated from control animals. Eotaxin 2 (CCL-24), which is known to influence eosinophil migration, was highly up-regulated in BAMs, but not Eotaxin-1 (CCL-11). Conversely, lung interstitial macrophages expressed high levels of CCL-11, but not CCL-24. Taken together, this study provides additional evidence to support the notion that M2 BAMs play a role in eosinophil and potentially other leukocyte migration patterns into asthmatic airways.
嗜酸性粒细胞和淋巴细胞向气道迁移是过敏性哮喘的一个标志;然而,肺泡巨噬细胞(BAMs)在这一炎症过程中的作用尚未完全阐明。本研究使用卵清蛋白(OVA)诱导的过敏性气道疾病(AAD)小鼠模型,通过微阵列和 qRT-PCR 评估 BAMs 中差异基因表达。OVA 致敏和激发的小鼠中,WBC、嗜酸性粒细胞增多、黏液积聚和杯状细胞增生明显增加,与 M2 型巨噬细胞的替代激活相关基因(如精氨酸酶 1、YM-1、YM-2、Resistin-like-α 和 EAR-11)表达增加相关。与哮喘相关的其他基因,如 FcγRIIb、MMP-14、CCL-8、CCL-17、ADAM-8、LTBR1、水通道蛋白-9 和 IL-7R,在 OVA 致敏/激发的动物中比在对照动物分离的 BAMs 中表达水平更高。已知影响嗜酸性粒细胞迁移的趋化因子 2(CCL-24)在 BAMs 中高度上调,但趋化因子 1(CCL-11)没有。相反,肺间质巨噬细胞表达高水平的 CCL-11,但不表达 CCL-24。综上所述,本研究为 M2 BAMs 参与嗜酸性粒细胞和潜在的其他白细胞向哮喘气道迁移模式的观点提供了更多证据。