Macrophage polarization is involved in liver fibrosis induced by β -adrenoceptor autoantibody.

Accumulating evidence suggests that liver injury can be induced by the over-expression of β -adrenergic receptors (β -ARs). High titers of autoantibodies specific to β -adrenergic receptors (β -AA) are detected in the sera of heart failure patients, potentially playing agonist-like roles. However, the role of β -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 and β -AA. A passive immunization model is established to assess the effect of β -AA on the liver. Subsequently, the effect of β -AA on macrophages is investigated . Results show that PBC patients have a high titer and ratio of β -AA, compared to controls. Liver injury and fibrosis are induced by β -AA. experiments with ROS probe demonstrate that β -AA induces macrophages to produce ROS and secrete TNFα. These effects can be partially reversed by metoprolol, a blocker for β -AR. Results from the transwell and phagocytosis assays show that β -AA promotes macrophage migration and phagocytosis. FCM tests suggest that β -AA induces the alteration of M1 rather than M2 markers in macrophages. Finally, the Annexin V/PI assay indicates that macrophage culture supernatants stimulated by β -AA cause hepatocyte apoptosis. Overall, these results suggest that β -AA is involved in PBC. The β -AA-induced activation, phagocytosis and phenotypic modification of macrophages may play an important role in the development of hepatic fibrosis and injury.