Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama 700-8558, Japan.
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Int J Mol Sci. 2020 Mar 7;21(5):1843. doi: 10.3390/ijms21051843.
Cross-linking of antigen-specific IgE bound to the high-affinity IgE receptor (FcεRI) on the surface of mast cells with multivalent antigens results in the release of mediators and development of type 2 inflammation. FcεRI expression and IgE synthesis are, therefore, critical for type 2 inflammatory disease development. In an attempt to clarify the relationship between eosinophilic chronic rhinosinusitis (ECRS) and mast cell infiltration, we analyzed mast cell infiltration at lesion sites and determined its clinical significance. Mast cells are positive for c-kit, and IgE in uncinated tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. The number of positive cells and clinicopathological factors were analyzed. Patients with ECRS exhibited high levels of total IgE serum levels and elevated peripheral blood eosinophil ratios. As a result, the number of mast cells with membranes positive for c-kit and IgE increased significantly in lesions forming NP. Therefore, we classified IgE-positive mast cells into two groups: membrane IgE-positive cells and cytoplasmic IgE-positive cells. The amount of membrane IgE-positive mast cells was significantly increased in moderate ECRS. A positive correlation was found between the membrane IgE-positive cells and the radiological severity score, the ratio of eosinophils, and the total serum IgE level. The number of cytoplasmic IgE-positive mast cells was significantly increased in moderate and severe ECRS. A positive correlation was observed between the cytoplasmic IgE-positive cells and the radiological severity score, the ratio of eosinophils in the blood, and the total IgE level. These results suggest that the process of mast cell internalization of antigens via the IgE receptor is involved in ECRS pathogenesis.
变应原特异性 IgE 与肥大细胞表面高亲和力 IgE 受体 (FcεRI) 交联,与多价抗原结合,导致介质释放和 2 型炎症的发展。因此,FcεRI 表达和 IgE 合成对于 2 型炎症性疾病的发展至关重要。为了阐明嗜酸性慢性鼻-鼻窦炎(ECRS)与肥大细胞浸润的关系,我们分析了病变部位的肥大细胞浸润,并确定了其临床意义。肥大细胞 c-kit 阳性,采用免疫组织化学法检测未卷曲组织(UT)和鼻息肉(NP)中的 IgE。分析阳性细胞数和临床病理因素。ECRS 患者血清总 IgE 水平升高,外周血嗜酸性粒细胞比例升高。结果,在形成 NP 的病变中,膜 c-kit 和 IgE 阳性的肥大细胞数量显著增加。因此,我们将 IgE 阳性肥大细胞分为两组:膜 IgE 阳性细胞和细胞质 IgE 阳性细胞。中度 ECRS 中膜 IgE 阳性肥大细胞的数量显著增加。膜 IgE 阳性细胞与放射学严重程度评分、嗜酸性粒细胞比例和总血清 IgE 水平呈正相关。中度和重度 ECRS 中细胞质 IgE 阳性肥大细胞的数量显著增加。细胞质 IgE 阳性细胞与放射学严重程度评分、血液中嗜酸性粒细胞比例和总 IgE 水平呈正相关。这些结果表明,通过 IgE 受体内化抗原的肥大细胞过程参与了 ECRS 的发病机制。