β-Adrenergic agonist modulation of monocyte adhesion to airway epithelial cells in vitro

Abstract

β-Adrenergic agonists are commonly used in the treatment of obstructive airway diseases and are known to modulate cAMP-dependent processes of airway epithelial cells. However, little is known regarding the ability of cAMP-dependent mechanisms to influence cell-cell interactions within the airway. Thus we investigated the role of the β-adrenergic agonist isoproterenol in modulating the ability of human bronchial epithelial cells to support the adhesion of THP-1 cells, a monocyte/macrophage cell line, in vitro. We demonstrated that pretreatment of human bronchial epithelial cells (HBECs) with 10 μM isoproterenol or 100 μM salbutamol augments the adhesion of fluorescently labeled THP-1 cells to HBEC monolayers by ∼40–60%. The increase in THP-1 cell adhesion occurred with 10 min of isoproterenol pretreatment of HBECs and gradually declined but persisted with up to 24 h of isoproterenol exposure. Exposure of THP-1 cells to isoproterenol or salbutamol before the adhesion assays did not result in an increase in adhesion to HBECs, suggesting that the isoproterenol modulation was primarily via changes in epithelial cells. A specific protein kinase A inhibitor, KT-5720, inhibited subsequent isoproterenol augmentation of THP-1 cell adhesion, further supporting the role of cAMP-dependent mechanisms in modulating THP-1 cell adhesion to HBECs.