Cui Tailin, Kusunose Masahiko, Hamada Atsuhide, Ono Masahide, Miyamura Mitsuhiko, Yoshioka Saburo, Kyotani Shojiro, Nishioka Yutaka
Department of Pharmacy, Kochi Medical School Hospital, Japan.
Biol Pharm Bull. 2003 Jul;26(7):959-63. doi: 10.1248/bpb.26.959.
A large number of studies have demonstrated that the presence of eosinophils in the lungs of patients with pulmonary fibrosis correlates with poor prognosis or resistance to therapy. However, direct evidence of the relationship between the influx of eosinophil and pulmonary fibrosis has not yet been described experimentally. In this article, pulmonary fibrosis was induced by different doses of bleomycin (BLM) and using different aged rats. On selected days afterwards, the lungs were lavaged and harvested for analyzing fibrosis, eosinophil influx and cytokine expression. There was a significant relationship between eosinophilia and the pulmonary fibrosis (r=0.98, p<0.01). In spite of the fact that there was no significant increase in hydroxyproline of the lung, eosinophil influxes of bronchoalveolar lavage fluid (BALF) was maximal 7 d after BLM administration. Moreover, there were similar patterns among transforming growth factor beta (TGF)-beta(1), hepatocyte growth factor (HGF) and eosinophil influx of BALF in that they were dependent on dose of BLM and age. These findings, taken together, have suggested the causal correlation of eosinophilia during the early stage with subsequent pulmonary fibrosis. The possible role of eosinophils in the pathogenesis of pulmonary fibrosis might contribute to not only TGF-beta(1) but also HGF production.
大量研究表明,肺纤维化患者肺部存在嗜酸性粒细胞与预后不良或治疗抵抗相关。然而,嗜酸性粒细胞浸润与肺纤维化之间关系的直接证据尚未通过实验得到描述。在本文中,使用不同剂量的博来霉素(BLM)并选用不同年龄的大鼠诱导肺纤维化。在随后选定的日子里,对肺进行灌洗并取材,用于分析纤维化、嗜酸性粒细胞浸润和细胞因子表达。嗜酸性粒细胞增多与肺纤维化之间存在显著相关性(r = 0.98,p < 0.01)。尽管肺组织羟脯氨酸没有显著增加,但博来霉素给药后7天支气管肺泡灌洗液(BALF)中的嗜酸性粒细胞浸润达到最大值。此外,转化生长因子β(TGF)-β1、肝细胞生长因子(HGF)和BALF中嗜酸性粒细胞浸润之间存在相似的模式,即它们依赖于博来霉素的剂量和年龄。综合这些发现,提示早期嗜酸性粒细胞增多与随后的肺纤维化存在因果关联。嗜酸性粒细胞在肺纤维化发病机制中的可能作用可能不仅有助于TGF-β1的产生,也有助于HGF的产生。