Cutting Edge: CLEC5A Mediates Macrophage Function and Chronic Obstructive Pulmonary Disease Pathologies.
Cutting Edge: CLEC5A Mediates Macrophage Function and Chronic Obstructive Pulmonary Disease Pathologies.
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DOI：
10.4049/jimmunol.1500978
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发表时间：
2016-04-15
期刊：
影响因子：
--
通讯作者：
Borchers MT
中科院分区：
文献类型：
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作者：
Wortham BW;Eppert BL;Flury JL;Garcia SM;Donica WR;Osterburg A;Joyce-Shaikh B;Cua DJ;Borchers MT
慢性阻塞性肺疾病（COPD）是一种毁灭性疾病，目前尚无有效的治疗方法。我们研究了c型凝集素受体CLEC5A在COPD小鼠模型中巨噬细胞活化和肺发病机制中的作用。我们证明CLEC5A在长期暴露于香烟烟雾（CS）的小鼠和人类吸烟者的肺泡巨噬细胞上表达。我们还发现，在cs暴露的小鼠中，clec5a介导的巨噬细胞激活可以单独增强细胞因子的精化，也可以与LPS或GM-CSF联合使用。此外，通过使用CLEC5A缺陷小鼠，我们证明了cs诱导的巨噬细胞反应是由CLEC5A介导的，并且CLEC5A是炎症、促炎细胞因子表达和空域扩大的发展所必需的。这些发现提示了一种新的机制，在CS暴露下促进气道炎症和病理反应，并确定了CLEC5A作为治疗性控制COPD发病机制的新靶点。
Chronic Obstructive Pulmonary Disease (COPD) is a devastating disease with no effective therapies. We investigated the role of the C-type lectin receptor, CLEC5A, in macrophage activation and pulmonary pathogenesis in a mouse model of COPD. We demonstrate that CLEC5A is expressed on alveolar macrophages in mice exposed long-term to cigarette smoke (CS) and in human smokers. We also show that CLEC5A-mediated activation of macrophages enhanced cytokine elaboration alone, and in combination with LPS or GM-CSF in CS-exposed mice. Furthermore, using Clec5a-deficient mice, we demonstrate that CS-induced macrophage responsiveness is mediated by CLEC5A and CLEC5A is required for the development of inflammation, proinflammatory cytokine expression and airspace enlargement. These findings suggest a novel mechanism that promotes airway inflammation and pathologies in response to CS exposure and identifies CLEC5A as a novel target for the therapeutic control of COPD pathogenesis.