Terada N, Hamano N, Kim W J, Hirai K, Nakajima T, Yamada H, Kawasaki H, Yamashita T, Kishi H, Nomura T, Numata T, Yoshie O, Konno A
Department of Otorhinolaryngology, Chiba University School of Medicine, Chiba, Japan.
Am J Respir Crit Care Med. 2001 Aug 15;164(4):575-9. doi: 10.1164/ajrccm.164.4.2009046.
Eotaxin (CCL11) is a potent eosinophil chemoattractant belonging to the C-C chemokine. To evaluate the role of eotaxin in eosinophilic inflammation in nasal mucosa, we investigated the levels of eosinophil chemoattractants in nasal lavage fluids obtained after antigen challenge, compared with eosinophil counts and eosinophil protein X (EPX) levels. In subjects with allergic rhinitis, allergen challenge led to parallel increases in eosinophil counts, levels of EPX, and eotaxin concentrations in nasal lavage fluid. The levels of eotaxin in lavage samples showed strong correlation with lavage levels of eosinophil counts and EPX. Normal subjects had few, if any, eosinophils and EPX as well as the measured parameters in their nasal lavage fluids before and after antigen challenge. In our experiments of eosinophil endothelial transmigration (TEM) assay using the nasal microvascular endothelial cells, eotaxin showed the most potent effect among various eosinophil chemoattractants. In addition, treatment of eosinophils with anti-CCR-3 mAb significantly blocked eosinophil TEM induced by homogenate of nasal mucosa. These results indicate that eotaxin has an important role in eosinophil-dependent inflammation in nasal mucosa and suggest that blocking eotaxin or CCR-3 might be useful for new therapeutic tools of allergic rhinitis.
嗜酸性粒细胞趋化因子(CCL11)是一种属于C-C趋化因子的强效嗜酸性粒细胞趋化剂。为了评估嗜酸性粒细胞趋化因子在鼻黏膜嗜酸性粒细胞炎症中的作用,我们检测了抗原激发后鼻灌洗液中嗜酸性粒细胞趋化剂的水平,并与嗜酸性粒细胞计数和嗜酸性粒细胞蛋白X(EPX)水平进行比较。在变应性鼻炎患者中,变应原激发导致鼻灌洗液中嗜酸性粒细胞计数、EPX水平和嗜酸性粒细胞趋化因子浓度平行升高。灌洗样本中嗜酸性粒细胞趋化因子的水平与嗜酸性粒细胞计数和EPX的灌洗水平密切相关。正常受试者在抗原激发前后,鼻灌洗液中几乎没有嗜酸性粒细胞和EPX,以及所检测的参数。在我们使用鼻微血管内皮细胞进行嗜酸性粒细胞内皮迁移(TEM)试验的实验中,嗜酸性粒细胞趋化因子在各种嗜酸性粒细胞趋化剂中显示出最有效的作用。此外,用抗CCR-3单克隆抗体处理嗜酸性粒细胞可显著阻断鼻黏膜匀浆诱导的嗜酸性粒细胞TEM。这些结果表明,嗜酸性粒细胞趋化因子在鼻黏膜嗜酸性粒细胞依赖性炎症中起重要作用,并提示阻断嗜酸性粒细胞趋化因子或CCR-3可能是变应性鼻炎新的治疗手段。