Macrophage polarization is involved in liver fibrosis induced byβ_(1)-adrenoceptor autoantibody  

作　　者：Ye Wu Xiongxiong Fan Haicun Yu Jingyi Liu Yanru Duan Suli Zhang Li Yan Yunhui Du Huirong Liu 

机构地区：[1]Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China [2]Beijing key laboratory of metabolic disorder related cardiovascular disease,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China [3]Zhengzhou Central Hospital affiliated of Zhengzhou University,Zhengzhou 450000,China [4]Shanxi Cardiovascular Hospital,Cardiac Care Unit,Taiyuan 030024,China [5]Department of Pathophysiology,Institute of Basic Medical Science,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100005,China [6]Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart,Lung and Blood Vessel Diseases,Beijing100029,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第8期1100-1112,共13页生物化学与生物物理学报（英文版）

基　　金：the grants from the National Natural Science Foundation of China(Nos.81970334 and 81770393 to H.L.)。

摘　　要：Accumulating evidence suggests that liver injury can be induced by the over-expression ofβ_(1)-adrenergic receptors(β_(1)-ARs).High titers of autoantibodies specific toβ_(1)-adrenergic receptors(β_(1)-AA)are detected in the sera of heart failure patients,potentially playing agonist-like roles.However,the role ofβ_(1)-AA in liver function has not been characterized.In this study,we collect the sera of primary biliary cholangitis(PBC)patients,a condition which easily develops into liver fibrosis,and analyze the relationship between PBC andβ_(1)-AA.A passive immunization model is established to assess the effect ofβ_(1)-AA on the liver.Subsequently,the effect ofβ_(1)-AA on macrophages is investigated in vitro.Results show that PBC patients have a high titer and ratio ofβ_(1)-AA,compared to controls.Liver injury and fibrosis are induced byβ_(1)-AA.In vitro experiments with ROS probe demonstrate thatβ_(1)-AA induces macrophages to produce ROS and secrete TNFα.These effects can be partially reversed by metoprolol,a blocker forβ_(1)-AR.Results from the transwell and phagocytosis assays show thatβ_(1)-AA promotes macrophage migration and phagocytosis.FCM tests suggest thatβ_(1)-AA induces the alteration of M1 rather than M2 markers in macrophages.Finally,the Annexin V/PI assay indicates that macrophage culture supernatants stimulated byβ_(1)-AA cause hepatocyte apoptosis.Overall,these results suggest thatβ_(1)-AA is involved in PBC.Theβ_(1)-AA-induced activation,phagocytosis and phenotypic modification of macrophages may play an important role in the development of hepatic fibrosis and injury.

关 键 词：β_(1)-adrenergic receptor AUTOANTIBODY hepatic fibrosis MACROPHAGES 

分 类 号：R575.2[医药卫生—消化系统]