Blight Brennan J, Gill Amarbir S, Sumsion Jorgen S, Pollard Chelsea E, Ashby Shaelene, Oakley Gretchen M, Alt Jeremiah A, Pulsipher Abigail
Division of Otolaryngology-Head and Neck Surgery, Rhinology-Sinus and Skull Base Surgery Program, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA.
J Asthma Allergy. 2021 May 27;14:585-593. doi: 10.2147/JAA.S307197. eCollection 2021.
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.
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.
Integrin and ICAM genes were significantly elevated in the blood (<0.001 to <0.05) and sinuses (<0.0003 to <0.05) of patients with CRSwNP compared to controls. Strong positive correlations of genes expressed in the blood (<0.01 to <0.05) and sinuses (<0.01) were observed between , and . ITGAM-, ITGB2-, ICAM-3-, and ICAM-3/ITGB2-positive cell counts were significantly increased in CRSwNP compared to controls (<0.0001 to <0.04), and a positive correlation between ICAM-3/ITGB2- and ITGAM-positive cell counts was observed (<0.02).
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.
伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）主要特征为嗜酸性粒细胞和2型辅助性T细胞（Th2）主导的炎症。整合素和细胞间黏附分子（ICAM）是细胞黏附分子（CAM）的超家族，可促进免疫细胞的募集和运输，并参与协调哮喘中嗜酸性粒细胞和Th2细胞的黏附及信号传导。然而，CAM在CRSwNP中的作用仍知之甚少。本研究的目的是描述CAM的全身和局部表达特征，并确定哪些CAM可能参与CRSwNP的病理过程。
采用前瞻性观察研究，纳入CRSwNP患者（n = 32）和对照组（n = 15）的外周血及筛前组织。进行多重基因分析和Pearson相关性分析，以确定全身和局部表达的CAM之间的关联。基于基因表达结果，对鼻窦组织中表达整合素ITGAM、ITGAX和ITGB2以及ICAM-3的细胞进行免疫组化评估和定量，以比较局部蛋白表达模式。
与对照组相比，CRSwNP患者血液（<0.001至<0.05）和鼻窦（<0.0003至<0.05）中的整合素和ICAM基因显著升高。观察到血液（<0.01至<0.05）和鼻窦（<0.01）中表达的基因之间存在强正相关。与对照组相比，CRSwNP中ITGAM、ITGB2、ICAM-3和ICAM-3/ITGB2阳性细胞计数显著增加（<0.0001至<0.04），且观察到ICAM-3/ITGB2与ITGAM阳性细胞计数之间呈正相关（<0.02）。
CRSwNP中ITGAM、ITGB2和ICAM-3的全身和局部表达显著上调，提示整合素复合物ITGAM/ITGB2和ICAM-3在CRSwNP炎症介导的信号传导中发挥潜在作用。
