Abstract
An imbalance in M1/M2 polarization is linked to the pathogenesis of immune thrombocytopenia (ITP). Terbutaline, a β2-adrenergic receptor agonist, can significantly increase the percentage of Tregs, attenuating thrombocytopenia in ITP. The effect of terbutaline on M1/M2 polarization in ITP remains uncertain. This study aimed to elucidate the connection between splenic sympathetic nerves and macrophage polarization and to assess the effect of terbutaline on macrophages in ITP. Peripheral blood-derived CD14+ monocytes were isolated from ITP patients and healthy donors and cultured in vitro. Spleen-derived macrophages were isolated from murine ITP models. Flow cytometry was used to analyze the percentages of M1 and M2 macrophages, assess the expression of macrophage markers, and perform in vitro phagocytosis assays. Targeted and nontargeted quantitative metabolomic analyses of amino acids in macrophages were conducted. Passive ITP models were used to examine the therapeutic benefits of terbutaline and its ability to modulate macrophage polarization. Decreased sympathetic nerve fibers and an imbalance in macrophage polarization were observed in the spleens of ITP mice. Sympathectomy aggravated the imbalance of splenic macrophage polarization and decreased platelet counts in mice. Recombinant high-mobility group box 1 (HMGB1) offset the altered polarization and platelet phagocytosis by splenic macrophages from ITP mice induced by terbutaline. Terbutaline alleviated the abnormal polarization of macrophages from patients with ITP. Terbutaline increased platelet counts in passive ITP murine models. Our study preliminarily suggests that terbutaline has the potential to alter abnormal macrophage polarization and reduce platelet phagocytosis and that HMGB1 could be involved in the mechanism of ITP.