O'Dwyer David N, Ashley Shanna L, Moore Bethany B
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan;
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan; and.
Am J Physiol Lung Cell Mol Physiol. 2016 Sep 1;311(3):L590-601. doi: 10.1152/ajplung.00221.2016. Epub 2016 Jul 29.
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by accumulation of extracellular matrix (ECM) and impaired gas exchange. The pathobiological mechanisms that account for disease progression are poorly understood but likely involve alterations in innate inflammatory cells, epithelial cells, and fibroblasts. Thus we seek to review the most recent literature highlighting the complex roles of neutrophils and macrophages as both promoters of fibrosis and defenders against infection. With respect to epithelial cells and fibroblasts, we review the data suggesting that defective autophagy promotes the fibrogenic potential of both cell types and discuss new evidence related to matrix metalloproteinases, growth factors, and cellular metabolism in the form of lactic acid generation that may have consequences for promoting fibrogenesis. We discuss potential cross talk between innate and structural cell types and also highlight literature that may help explain the limitations of current IPF therapies.
特发性肺纤维化（IPF）是一种进行性间质性肺病，其特征是细胞外基质（ECM）积聚和气体交换受损。导致疾病进展的病理生物学机制尚不清楚，但可能涉及先天性炎症细胞、上皮细胞和成纤维细胞的改变。因此，我们试图回顾最新的文献，突出中性粒细胞和巨噬细胞作为纤维化促进者和抗感染防御者的复杂作用。关于上皮细胞和成纤维细胞，我们回顾了表明自噬缺陷促进这两种细胞类型纤维化潜能的数据，并讨论了与基质金属蛋白酶、生长因子以及以乳酸生成形式存在的细胞代谢相关的新证据，这些可能对促进纤维化产生影响。我们讨论了先天性细胞和结构细胞类型之间潜在的相互作用，还突出了可能有助于解释当前IPF治疗局限性的文献。
