Pires Gisele V, Souza Heitor S P, Elia Celeste C S, Zaltman Cyrla, Carvalho Ana Teresa P, Tortori Claudio J A, Garrofé Henrique C, Lapa e Silva José Roberto
Department of Internal Medicine, School of Medicine, Multidisciplinary Laboratory of the Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Brazil.
Allergy Asthma Proc. 2004 Jul-Aug;25(4):253-9.
Eosinophils participate in the pathogenesis of inflammatory diseases of the respiratory tract and the gut. We investigated the constitutive presence of eosinophils and mononuclear cells in the macroscopically normal duodenal mucosa of patients with asthma and allergic rhinitis. Macroscopically normal duodenal specimens were obtained at routine endoscopy for upper gastrointestinal symptoms from 16 patients with asthma and 13 patients with allergic rhinitis. Twelve nonatopic patients with irritable bowel syndrome were studied as controls. Specimens were analyzed by immunohistochemistry using a panel of antibodies to human eosinophil cationic protein clone EG1 (EG1) and clone EG2 (EG2), anti-human interleukin (anti-hIL)-5, anti-hIL-4, anti-CD4, and anti-CD68. Significantly increased numbers of eosinophils stained with EG1 and EG2 were found in the duodenum of patients with asthma and allergic rhinitis compared with controls. IL-5+ cells and IL-4+ cells were detected in significantly increased numbers in the duodenal mucosa of patients with asthma and rhinitis compared with controls. Mononuclear cells expressing CD4 (helper T cells) and CD68 (macrophages) also were significantly increased in the duodenal mucosa of asthma and rhinitis compared with controls. Accumulation of eosinophils in conjunction with IL-4+ cells and IL-5+ cells in the noninflamed duodenal mucosa may reflect a predominant T helper cell subset 2 systemic immune response in patients with asthma and allergic rhinitis. The absence of intestinal inflammation despite the marked presence of cells implicated in the allergic inflammation suggests that local mechanisms might determine the state of nonresponsiveness in the gut mucosa of patients with asthma and allergic rhinitis.
嗜酸性粒细胞参与呼吸道和肠道炎症性疾病的发病机制。我们研究了哮喘和过敏性鼻炎患者宏观上正常的十二指肠黏膜中嗜酸性粒细胞和单核细胞的组成性存在情况。通过常规上消化道内镜检查,从16例哮喘患者和13例过敏性鼻炎患者中获取宏观上正常的十二指肠标本,这些患者均有上消化道症状。选取12例患有肠易激综合征的非特应性患者作为对照。使用一组针对人嗜酸性粒细胞阳离子蛋白克隆EG1(EG1)和克隆EG2(EG2)、抗人白细胞介素(抗-hIL)-5、抗-hIL-4、抗-CD4和抗-CD68的抗体,通过免疫组织化学对标本进行分析。与对照组相比,哮喘和过敏性鼻炎患者十二指肠中用EG1和EG2染色的嗜酸性粒细胞数量显著增加。与对照组相比,哮喘和鼻炎患者十二指肠黏膜中IL-5+细胞和IL-4+细胞的数量显著增加。与对照组相比,哮喘和鼻炎患者十二指肠黏膜中表达CD4(辅助性T细胞)和CD68(巨噬细胞)的单核细胞也显著增加。在未发炎的十二指肠黏膜中,嗜酸性粒细胞与IL-4+细胞和IL-5+细胞的聚集可能反映了哮喘和过敏性鼻炎患者中主要的辅助性T细胞2型全身免疫反应。尽管存在与过敏性炎症相关的明显细胞,但肠道未出现炎症,这表明局部机制可能决定了哮喘和过敏性鼻炎患者肠道黏膜的无反应状态。