How Adhesion Molecule Patterns Change While Neutrophils Traffic through the Lung during Inflammation
How Adhesion Molecule Patterns Change While Neutrophils Traffic through the Lung during Inflammation
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DOI：
10.1155/2019/1208086
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发表时间：
2019-01-01
影响因子：
4.6
通讯作者：
Reutershan, Joerg
中科院分区：
文献类型：
--
作者：
Konrad, Franziska M.;Wohlert, Julia;Reutershan, Joerg
在急性肺部炎症中，多形核细胞（PMNs）从循环中穿过跨内皮屏障进入肺动脉，随后经上皮迁移进入肺泡腔。尽管经过几十年的研究，这些迁移步骤被粘附分子和粘附分子的概念差异化地调节。目前粘附分子表达模式变化的知识主要来自体外研究或肺外器官系统的研究，其中粘附分子的调节显著不同。在肺部炎症的小鼠模型中，我们确定了9种相关的嗜酸性粘附分子在通过肺的不同隔室的途中的表达模式。我们使用了流式细胞术为基础的技术，允许描述的空间分布的粘附分子表达的中性粒细胞在其迁移过程中通过肺的细节。例如，在血管内隔室中发现了CD29的最高表达，突出了其对与内皮的初始粘附的影响。CD47在跨内皮迁移的晚期表达最高，而CD11b和CD54在间质表达最高。发现粘附分子CD 172a在跨上皮迁移中起关键作用。因此，表达可能与特定迁移步骤的功能影响相关。体外研究进一步证实了我们在体内的发现。总之，我们是第一个确定相关粘附分子在通过肺的不同隔室迁移时表达模式的变化。这些发现可能有助于进一步了解肺中性粒细胞运输的调节。
In acute pulmonary inflammation, polymorphonuclear cells (PMNs) pass a transendothelial barrier from the circulation into the lung interstitium followed by a transepithelial migration into the alveolar space. These migration steps are regulated differentially by a concept of adhesion molecules and remaindespite decades of researchincompletely understood. Current knowledge of changes in the expression pattern of adhesion molecules mainly derives from in vitro studies or from studies in extrapulmonary organ systems, where regulation of adhesion molecules differs significantly. In a murine model of lung inflammation, we determined the expression pattern of nine relevant neutrophilic adhesion molecules on their way through the different compartments of the lung. We used a flow cytometry-based technique that allowed describing spatial distribution of the adhesion molecules expressed on PMNs during their migration through the lung in detail. For example, the highest expression of CD29 was found in the intravascular compartment, highlighting its impact on the initial adhesion to the endothelium. CD47 showed its peak of expression on the later phase of transendothelial migration, whereas CD11b and CD54 expression peaked interstitial. A pivotal role for transepithelial migration was found for the adhesion molecule CD172a. Thereby, expression may correlate with functional impact for specific migration steps. In vitro studies further confirmed our in vivo findings. In conclusion, we are the first to determine the changes in expression patterns of relevant adhesion molecules on their migration through the different compartments of the lung. These findings may help to further understand the regulation of neutrophil trafficking in the lung.