Ponikau Jens U, Sherris David A, Kephart Gail M, Kern Eugene B, Congdon David J, Adolphson Cheryl R, Springett Margaret J, Gleich Gerald J, Kita Hirohito
Department of Otorhinolaryngology-Head and Neck Surgery, Mayo Clinic Rochester, Rochester, MN 55905, USA.
J Allergy Clin Immunol. 2005 Aug;116(2):362-9. doi: 10.1016/j.jaci.2005.03.049.
The mechanisms by which eosinophilic inflammation damages the epithelium and contributes to recurrent acute exacerbations in chronic rhinosinusitis (CRS) have not been fully elucidated.
We tested the hypotheses that eosinophils deposit toxic major basic protein (MBP) in the mucus and that MBP reaches concentrations able to damage the sinonasal epithelium.
Tissue specimens with mucus attached to the tissue were carefully collected from 22 patients with CRS and examined by using immunofluorescence staining for MBP. This immunofluorescence was digitally analyzed to determine the area covered by MBP and the intensity of the staining (estimating MBP concentration). Levels of MBP in extracts from nasal mucus were quantitated by means of RIA.
Heterogeneous eosinophilia was evident within tissue and mucus specimens. All tissue specimens showed intact eosinophils, but diffuse extracellular MBP deposition, as a marker of eosinophil degranulation, was rare. In contrast, all mucus specimens showed diffuse MBP throughout and abundant diffuse extracellular MBP deposition within clusters of eosinophils. Digitized analyses of MBP immunofluorescence revealed increased area coverage (P < .0001) in mucus compared with that seen in tissue. Estimated concentrations of MBP within the clusters suggested toxic levels. MBP concentrations in mucus extract reached 11.7 microg/mL; MBP was not detectable in healthy control subjects.
In patients with CRS, eosinophils form clusters in the mucus where they release MBP, which is diffusely deposited on the epithelium, a process not observed in the tissue. Estimated MBP levels far exceed those needed to damage epithelium from the luminal side and could predispose patients with CRS to secondary bacterial infections.
嗜酸性粒细胞炎症损伤上皮并导致慢性鼻-鼻窦炎（CRS）反复急性加重的机制尚未完全阐明。
我们检验了以下假设，即嗜酸性粒细胞在黏液中沉积有毒的主要碱性蛋白（MBP），且MBP达到能够损伤鼻窦上皮的浓度。
从22例CRS患者中仔细收集附有黏液的组织标本，并采用MBP免疫荧光染色进行检测。对该免疫荧光进行数字分析，以确定MBP覆盖的面积和染色强度（估计MBP浓度）。通过放射免疫分析对鼻黏液提取物中的MBP水平进行定量。
在组织和黏液标本中可见异质性嗜酸性粒细胞增多。所有组织标本中的嗜酸性粒细胞均完整，但作为嗜酸性粒细胞脱颗粒标志物的弥漫性细胞外MBP沉积很少见。相比之下，所有黏液标本均显示整个标本中有弥漫性MBP，且在嗜酸性粒细胞簇内有大量弥漫性细胞外MBP沉积。MBP免疫荧光的数字分析显示，与组织相比，黏液中的面积覆盖率增加（P <.0001）。嗜酸性粒细胞簇内估计的MBP浓度表明达到了有毒水平。黏液提取物中的MBP浓度达到11.7μg/mL；在健康对照者中未检测到MBP。
在CRS患者中，嗜酸性粒细胞在黏液中形成簇并释放MBP，MBP弥漫性沉积在上皮上，这一过程在组织中未观察到。估计的MBP水平远远超过从管腔侧损伤上皮所需的水平，可能使CRS患者易发生继发性细菌感染。
