β-Adrenergic stimulation increases macrophage CD14 expression and E. coli phagocytosis through PKA signaling mechanisms

CD14 is a glycoprotein that binds bacterial LPS in MO. It is an essential component of the phagocytic system and is increased in septic shock. Critical injury and sepsis result in elevated endogenous CA levels. CAs have a significant impact on MO inflammatory functions. We tested the hypothesis that β-adrenergic stimulation regulates CD14 expression and bacterial phagocytosis in BMO. Murine BMO stimulated with isoproterenol (>8 h) induced a dose-dependent increase in cell surface CD14 expression. Specific PKA inhibitor (H-89) and gene-silencing (siRNA) studies demonstrated the role of cAMP-dependent PKA in mediating this response. In addition, we observed a correlation between an isoproterenol-mediated increase in CD14 expression and live Escherichia coli uptake in BMO. Further, the essential role of CD14 in an isoproterenol-mediated increase in E. coli uptake was highlighted from experiments using CD14−/− mice. Moreover, the dose response of isoproterenol stimulation to CD14 expression and E. coli phagocytosis overlapped with similar EC50. Additionally, isoproterenol-mediated E. coli phagocytosis was prevented by H-89, suggesting that β-adrenergic stimulus in BMO increases CD14 expression and live E. coli phagocytosis through a common signaling pathway. Our studies indicate the potential impact of β-adrenergic agents on important innate immune functions.