Simon H U, Yousefi S, Schranz C, Schapowal A, Bachert C, Blaser K
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich.
J Immunol. 1997 Apr 15;158(8):3902-8.
Nasal polyps, which often occur in association with allergic rhinitis and asthma, are characterized by a marked infiltration of eosinophils. Using a method for detecting eosinophils with DNA strand breaks, we found direct evidence for inhibition of eosinophil apoptosis in this model of tissue eosinophilia. By using Southern blot analysis linked to reverse transcription-PCR, we detected a mRNA signal specific for IL-5 in all nasal polyps. The identification of IL-5 as a major eosinophil survival factor was confirmed by ELISA measurements using tissue homogenates. Moreover, immunohistochemical analysis of the nasal polyp tissues demonstrated that IL-5 was localized in lymphocytes, mast cells, and eosinophils. Treatment of the eosinophil-infiltrated tissue with neutralizing anti-IL-5 mAb induced eosinophil apoptosis and decreased tissue eosinophilia. Therefore, IL-5 may represent an important cytokine responsible for the delay of the death process in eosinophils in nasal polyps. In addition, a previously suggested IL-4-dependent specific recruitment of eosinophils into the inflamed tissue could be excluded by our studies. Taken together, these findings suggest a novel mechanism by which eosinophils specifically accumulate in pathologic human tissues.
鼻息肉常与过敏性鼻炎和哮喘相关，其特征为嗜酸性粒细胞显著浸润。使用一种检测有DNA链断裂的嗜酸性粒细胞的方法，我们在这种组织嗜酸性粒细胞增多模型中发现了嗜酸性粒细胞凋亡受抑制的直接证据。通过将Southern印迹分析与逆转录 - PCR相结合，我们在所有鼻息肉中检测到了IL - 5特异的mRNA信号。使用组织匀浆进行ELISA测量证实了IL - 5作为主要嗜酸性粒细胞存活因子的身份。此外，鼻息肉组织的免疫组化分析表明IL - 5定位于淋巴细胞、肥大细胞和嗜酸性粒细胞中。用中和性抗IL - 5单克隆抗体处理嗜酸性粒细胞浸润组织可诱导嗜酸性粒细胞凋亡并减轻组织嗜酸性粒细胞增多。因此，IL - 5可能是导致鼻息肉中嗜酸性粒细胞死亡过程延迟的一种重要细胞因子。此外，我们的研究排除了先前提出的IL - 4依赖的嗜酸性粒细胞特异性募集到炎症组织中的可能性。综上所述，这些发现提示了一种嗜酸性粒细胞在病理性人体组织中特异性积聚的新机制。
