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Cell Adhesion Molecules are Upregulated and May Drive Inflammation in Chronic Rhinosinusitis with Nasal Polyposis
Journal of Asthma and Allergy ( IF 3.2 ) Pub Date : 2021-05-27 , DOI: 10.2147/jaa.s307197
Brennan J Blight 1 , Amarbir S Gill 1 , Jorgen S Sumsion 1 , Chelsea E Pollard 1 , Shaelene Ashby 1 , Gretchen M Oakley 1 , Jeremiah A Alt 1 , Abigail Pulsipher 1
Affiliation  

Purpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly characterized by eosinophil- and T helper 2 cell (Th2)-biased inflammation. Integrins and intercellular adhesion molecules (ICAMs) are superfamilies of cell adhesion molecules (CAMs) that facilitate the recruitment and trafficking of immune cells and have been implicated in coordinating eosinophil and Th2 cell adhesion and signaling in asthma. The roles of CAMs in CRSwNP, however, remain poorly understood. The purpose of this study was to characterize the systemic and local expression of CAMs and identify which CAMs are potentially involved in CRSwNP pathology.
Materials and Methods: A prospective observational study was conducted using peripheral blood and anterior ethmoid tissues of patients with CRSwNP (n=32) and controls (n=15). Multiplex gene analysis and Pearson correlations were performed to identify associations between systemically and locally expressed CAMs. Based on the gene expression results, immunohistochemical evaluation and quantification of cells expressing integrins ITGAM, ITGAX, and ITGB2, as well as ICAM-3 in sinonasal tissues were conducted to compare local protein expression patterns.
Results: Integrin and ICAM genes were significantly elevated in the blood (p< 0.001 to p< 0.05) and sinuses (p< 0.0003 to p< 0.05) of patients with CRSwNP compared to controls. Strong positive correlations of genes expressed in the blood (p< 0.01 to p< 0.05) and sinuses (p< 0.01) were observed between ITGAM, ITGAX, ITGB2, and ICAM3. ITGAM-, ITGB2-, ICAM-3-, and ICAM-3/ITGB2-positive cell counts were significantly increased in CRSwNP compared to controls (p< 0.0001 to p< 0.04), and a positive correlation between ICAM-3/ITGB2- and ITGAM-positive cell counts was observed (p< 0.02).
Conclusion: The systemic and local expression of ITGAM, ITGB2, and ICAM-3 is significantly upregulated in CRSwNP, suggesting that integrin complex ITGAM/ITGB2 and ICAM-3 serve a potential role in inflammation-mediated signaling in CRSwNP.

Keywords: integrins, intercellular adhesion molecule 3, macrophage-1 antigen, Th2 pathophysiology, transcriptional analysis, allergy, asthma


中文翻译:

细胞粘附分子上调并可能导致慢性鼻窦炎伴鼻息肉病的炎症

目的:慢性鼻窦炎伴鼻息肉 (CRSwNP) 的主要特征是嗜酸性粒细胞和辅助性 T 细胞 (Th2) 偏向性炎症。整合素和细胞间粘附分子 (ICAM) 是细胞粘附分子 (CAM) 的超家族,可促进免疫细胞的招募和运输,并参与协调哮喘中的嗜酸性粒细胞和 Th2 细胞粘附和信号传导。然而,CAM 在 CRSwNP 中的作用仍然知之甚少。本研究的目的是表征 CAM 的全身和局部表达,并确定哪些 CAM 可能参与 CRSwNP 病理学。
材料和方法:使用 CRSwNP 患者 (n=32) 和对照者 (n=15) 的外周血和筛前组织进行了一项前瞻性观察性研究。进行多重基因分析和 Pearson 相关性以确定系统和局部表达的 CAM 之间的关联。根据基因表达结果,对鼻腔组织中表达整合素ITGAM、ITGAX和ITGB2以及ICAM-3的细胞进行免疫组织化学评估和定量,以比较局部蛋白表达模式。
结果:与对照组相比,CRSwNP 患者的血液(p < 0.001 至p < 0.05)和鼻窦(p < 0.0003 至p < 0.05)中整合素和 ICAM 基因显着升高。在ITGAM、ITGAX、ITGB2ICAM3之间观察到血液( p <0.01 至p <0.05)和鼻窦(p <0.01)中表达的基因呈强正相关。与对照组相比,CRSwNP 中 ITGAM-、ITGB2-、ICAM-3- 和 ICAM-3/ITGB2- 阳性细胞计数显着增加(p < 0.0001 至p < 0.04),并且 ICAM-3/ITGB2- 之间呈正相关。观察到 ITGAM 阳性细胞计数 ( p < 0.02)。结论: ITGAM、ITGB2 和 ICAM-3 在 CRSwNP 中的全身和局部表达显着上调,表明整合素复合物 ITGAM/ITGB2 和 ICAM-3 在 CRSwNP 炎症介导的信号传导中发挥潜在作用。关键词:整合素, 细胞间粘附分子3, 巨噬细胞1抗原, Th2病理生理学, 转录分析, 过敏, 哮喘


更新日期:2021-05-27
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