摘要
巨噬细胞是一类具有多能性和可塑性的免疫细胞群体,在体内外不同的微环境作用下,可分化成不同的表型。在IPF发展过程中主要有AM与IM 2类,二者在不同发病阶段向不同细胞表型极化,其极化表型包括M1型巨噬细胞和M2型巨噬细胞。在肺纤维化炎症早期,M1型比例的升高有利于清除病原微生物,推进炎症的进展;在纤维化后期,M2型巨噬细胞数量的增加可以抑制炎性反应,同时可以促进纤维化的降解。在IPF中,M1,M2极化机制与TGF-β1/Smad关系密切,其中极化通路TGF-β1/Smad在肝纤维化、肾纤维化、心肌纤维化、瘢痕、肿瘤等多种疾病中均具有重要的调控作用。阻断Smad3,4对TGF-β1的信号传导有利于抑制AM的极化,进而有助于抑制IPF进展。
Macrophages are a group of immune cells with pluripotency and plasticity that can differentiate into different phenotypes under different microenvironments in vitro and in vivo. In the development of pulmonary fibrosis,there are alveolar macrophages and interstitial macrophages,which are polarized to different cell phenotypes at different stages of development. And their polarized phenotypes include M1 macrophages and M2 macrophages. In the inflammation early stages of pulmonary fibrosis,the increase of classical activated macrophages are helpful to clear pathogenic microorganisms and promote the progress of inflammation. In the fibrosis stage,the alternatively activated macrophages increased,which inhibiting the inflammatory reaction or directly promoting tissue fibrosis,on the other hand,it also promoting the fibrosis degradation. To clarify the polarization and polarization mechanisms of macrophages in pulmonary fibrosis will be conducive to the treatment of pulmonary fibrosis. In IPF,the polarization mechanism of M1 and M2 is closely related to TGF-β1/Smad. TGF-β1/Smad pathway plays an important regulatory role in liver fibrosis,renal fibrosis,myocardial fibrosis,scars,tumors and other diseases. Blocking the signaling of TGF-β1 by Smad3 and Smad4 is beneficial to inhibit the polarization of AM,which in turn helps to inhibit the progression of IPF.
引文
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