A2B Adenosine Receptor Expression by Myeloid Cells Is Proinflammatory in Murine Allergic-Airway Inflammation
A2B Adenosine Receptor Expression by Myeloid Cells Is Proinflammatory in Murine Allergic-Airway Inflammation
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DOI：
10.4049/jimmunol.1201207
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发表时间：
2012-10-01
影响因子：
4.4
通讯作者：
Remick, Daniel G.
中科院分区：
文献类型：
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作者：
Belikoff, Bryan G.;Vaickus, Louis J.;Remick, Daniel G.
哮喘是一种慢性病，发病率高，医疗费用高，蟑螂过敏原是城市儿童哮喘的一个确定原因。更好地了解参与促进肺部炎症的细胞类型可以为慢性肺部疾病的治疗提供新的靶点。由于其在调节髓细胞依赖性炎症过程中的作用，我们在小鼠哮喘样肺部炎症的蟑螂过敏原模型中检测了A(2B) R在髓细胞中的表达。在致敏小鼠中，系统性和髓系组织特异性A(2B) R缺失显著降低了最终致敏原攻击后肺部炎症细胞募集、气道粘蛋白产生和促炎细胞因子分泌。A(2B) R缺乏导致th2型气道反应显著减少，肺嗜酸性粒细胞减少，但中性粒细胞不增加，肺IL-4、IL-5和IL-13的产生减少。趋化因子分析表明，eotaxin 1和eotaxin 2的分泌对反复过敏原攻击的反应依赖于髓细胞A(2B) R。相比之下，在髓样细胞A(2B) R缺陷小鼠中，CXC趋化因子角化细胞衍生趋化因子和MIP-2的水平没有差异，这加强了A(2B) R参与th2型气道炎症的发展。在系统性和髓系组织特异性A(2B) R缺失小鼠系中，促炎tnf - α、ifn - γ和IL-17的分泌也减少。我们的研究结果表明，髓细胞中A(2B) R表达的th2型优势是哮喘样肺部炎症发展的机制之一。免疫学杂志，2012,19(3):3707-3713。
Asthma is a chronic condition with high morbidity and healthcare costs, and cockroach allergens are an established cause of urban pediatric asthma. A better understanding of cell types involved in promoting lung inflammation could provide new targets for the treatment of chronic pulmonary disease. Because of its role in regulating myeloid cell-dependent inflammatory processes, we examined A(2B) R expression by myeloid cells in a cockroach allergen model of murine asthma-like pulmonary inflammation. Both systemic and myeloid tissue-specific A(2B) R deletion significantly decreased pulmonary inflammatory cell recruitment, airway mucin production, and proinflammatory cytokine secretion after final allergen challenge in sensitized mice. A(2B) R deficiency resulted in a dramatic reduction on Th2-type airways responses with decreased pulmonary eosinophilia without augmenting neutrophilia, and decreased lung IL-4, IL-5, and IL-13 production. Chemokine analysis demonstrated that eotaxin 1 and 2 secretion in response to repeated allergen challenge is myeloid cell A(2B) R dependent. In contrast, there were no differences in the levels of the CXC chemokines keratinocyte-derived chemokine and MIP-2 in the myeloid cell A(2B) R-deficient mice, strengthening A(2B) R involvement in the development of Th2-type airways inflammation. Proinflammatory TNF-alpha, IFN-gamma, and IL-17 secretion were also reduced in systemic and myeloid tissue-specific A(2B) R deletion mouse lines. Our results demonstrate Th2-type predominance for A(2B) R expression by myeloid cells as a mechanism of development of asthma-like pulmonary inflammation. The Journal of Immunology, 2012, 189: 3707-3713.