Gharaee-Kermani M, Phan S H
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Int J Mol Med. 1998 Jan;1(1):43-53.
Pulmonary fibrosis is commonly characterized by inflammation of the alveolar wall, leading to derangement of normal alveolar architecture, and interstitial as well as intra-alveolar fibrosis. The process involves cellular interactions via a complex cytokine network and heightened collagen gene expression with abnormal deposition in the lung. Recent studies have identified a myriad of cytokines with potential roles in pulmonary fibrosis. Based on in vivo antibody neutralization studies, important roles for tumor necrosis á (TNFá), macrophage inflammatory protein 1á (MIP-1á) and transforming growth factor (TGF), have been established. The recent demonstration that the eosinophil is a major source for several of these key pro-fibrogenic cytokines during the early stages of fibrosis, strongly suggest a role for the eosinophil in pulmonary fibrosis. In vitro, eosinophils can elaborate factors capable of stimulating fibroblast proliferation, and their presence in lungs undergoing many forms of pulmonary fibrosis has been well documented. Further support for a role for eosinophils in pulmonary fibrosis are suggested by clinical data showing a correlation between lung eosinophil count and a poor prognosis and decreased responsiveness to therapy. This review will focus on the recent findings, which suggest novel potential roles for the eosinophil in the pathogenesis of pulmonary fibrosis.
肺纤维化的常见特征是肺泡壁炎症，导致正常肺泡结构紊乱，以及间质和肺泡内纤维化。该过程涉及通过复杂的细胞因子网络进行的细胞相互作用，以及肺中胶原基因表达增强和异常沉积。最近的研究已经确定了无数在肺纤维化中具有潜在作用的细胞因子。基于体内抗体中和研究，肿瘤坏死因子α（TNFα）、巨噬细胞炎性蛋白1α（MIP-1α）和转化生长因子（TGF）的重要作用已得到证实。最近的研究表明，在纤维化早期，嗜酸性粒细胞是这些关键促纤维化细胞因子中几种的主要来源，这强烈表明嗜酸性粒细胞在肺纤维化中起作用。在体外，嗜酸性粒细胞可以产生能够刺激成纤维细胞增殖的因子，并且它们在经历多种形式肺纤维化的肺中的存在已得到充分记录。临床数据显示肺嗜酸性粒细胞计数与预后不良以及对治疗的反应性降低之间存在相关性，这进一步支持了嗜酸性粒细胞在肺纤维化中起作用的观点。本综述将重点关注最近的研究结果，这些结果表明嗜酸性粒细胞在肺纤维化发病机制中具有新的潜在作用。
