Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.
Int Forum Allergy Rhinol. 2012 Mar-Apr;2(2):122-5. doi: 10.1002/alr.21004. Epub 2011 Dec 29.
P-glycoprotein (P-gp) is a 170-kDa transmembrane glycoprotein encoded by the MDR1 (ABCB1) gene and is constitutively expressed on lower airway epithelium. P-gp has been shown to function as an immunomodulator regulating efflux of T-helper 1/T-helper 2 (Th1/Th2) cytokines from its host cell; however, its association with sinonasal inflammation has not been described. The purpose of this study is to determine the pattern and degree of epithelial P-gp expression in chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP) or CRS without nasal polyposis (CRSsNP).
Institutional Review Board (IRB)-approved study utilizing sinus, septal, and inferior turbinate mucosa in patients with no disease, CRS, and CRSwNP (n = 4 each). Quantitative fluorescent immunohistochemistry (Q-FIHC) was performed using an anti-P-gp antibody and a secondary fluorescein isothiocyanate (FITC)-conjugated Fc specific fragment. Protein expression was quantified by calculating the epithelial to nonspecific background intensity ratio (4 images/subsite). Scores less than 1 suggested negligible expression. Staining ratios between patient groups and subsites were compared using a 2-tailed Student t test.
Among the sinus mucosa, P-gp expression in CRSwNP (1.570 ± 0.354) was significantly greater than both CRS (1.224 ± 0.248) and control (0.762 ± 0.128) (p < 0.001, p = 0.002; respectively). CRS scores were significantly greater than control (p = 0.002). Among the septal mucosa, there was no significant difference between CRSwNP (0.914 ± 0.264), CRS (1.126 ± 0.476), or control (0.966 ± 0.327). Among the inferior turbinate mucosa, there was no significant difference between CRSwNP (1.047 ± 0.157), CRS (1.099 ± 0.362), or control (0.824 ± 0.181).
MDR1/P-gp is overexpressed in the epithelial layer of sinus mucosa in patients with both CRSwNP and CRS relative to other sinonasal subsites. Expression in healthy mucosa is negligible. Given its known immunomodulatory function this suggests that P-gp may play a role in the pathogenesis or maintenance of chronic sinonasal inflammation.
P-糖蛋白（P-gp）是一种 170kDa 的跨膜糖蛋白，由 MDR1（ABCB1）基因编码，在低气道上皮细胞中持续表达。已经证明 P-gp 作为一种免疫调节剂，调节辅助性 T 细胞 1/辅助性 T 细胞 2（Th1/Th2）细胞因子从宿主细胞中的流出；然而，其与鼻-鼻窦炎症的关联尚未被描述。本研究的目的是确定慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）或无鼻息肉的慢性鼻-鼻窦炎（CRSsNP）中上皮 P-gp 表达的模式和程度。
利用无疾病、CRS 和 CRSwNP 患者的鼻窦、鼻中隔和下鼻甲黏膜进行机构审查委员会（IRB）批准的研究（每组各 4 例）。使用抗 P-gp 抗体和二级荧光异硫氰酸荧光素（FITC）缀合的 Fc 特异性片段进行定量荧光免疫组织化学（Q-FIHC）。通过计算上皮与非特异性背景强度比（每个部位 4 张图像）来量化蛋白表达。评分小于 1 表明表达可忽略不计。使用双尾学生 t 检验比较患者组和部位之间的染色比。
在鼻窦黏膜中，CRSwNP 中的 P-gp 表达（1.570 ± 0.354）明显高于 CRS（1.224 ± 0.248）和对照组（0.762 ± 0.128）（p < 0.001，p = 0.002；分别）。CRS 评分明显高于对照组（p = 0.002）。在鼻中隔黏膜中，CRSwNP（0.914 ± 0.264）、CRS（1.126 ± 0.476）和对照组（0.966 ± 0.327）之间无显著差异。在下鼻甲黏膜中，CRSwNP（1.047 ± 0.157）、CRS（1.099 ± 0.362）和对照组（0.824 ± 0.181）之间无显著差异。
与其他鼻-鼻窦部位相比，MDR1/P-gp 在 CRSwNP 和 CRS 患者的鼻窦黏膜上皮层中过度表达。健康黏膜中的表达可忽略不计。鉴于其已知的免疫调节功能，这表明 P-gp 可能在慢性鼻-鼻窦炎症的发病机制或维持中发挥作用。
