Alpha2B-Adrenergic Receptor Regulates Neutrophil Recruitment in MSU-Induced Peritoneal Inflammation

Gout is one of the most common metabolic disorders in human. Previous studies have shown that the disease activity is closely associated with sympathetic nervous system (SNS). α(2B)-adrenergic receptor (α(2B)AR), a subtype of α2 adrenergic receptor, plays a critical role in many diseases. However, the role of α(2B)AR in the pathogenesis of gout remains unclear. Here, we assessed the role of α(2B)AR in the monosodium urate (MSU) crystals-induced peritonitis that mimics human gout by using the α(2B)AR-overexpressing mice (α(2B)AR-Tg). We found that the number of recruited neutrophils was significantly increased in the α(2B)AR-Tg mice after MSU treatment, when compared with wild type mice. In contrast, the number of macrophages was not changed. Importantly, there is no difference in the IL-1β levels and caspase-1 activity between wild type and α(2B)AR-Tg mice in the gout animal model. Notably, the enhanced neutrophil migration in α(2B)AR-Tg mice was dependent on the α(2B)AR overexpression in neutrophils, but not resulted from other tissues or cells with α(2B)AR overexpression. In conclusion, our data provide a direct evidence that α(2B)AR plays a critical role in neutrophil migration and MSU-induced inflammation.