Chronic β-adrenoceptor Antagonists Upregulate the Rat Alveolar Macrophage Adrenergic System Through the β₁-Subtype

Abstract

Background: Previous studies demonstrate that macrophages synthesis and release catecholamines, which regulate the immune responses in an autocrine manner. These responses are mediated in part by β-adrenoceptors expressed on macrophages. Some β-adrenoceptor antagonists are commonly used in clinical conditions. Here we investigated whether the chronic administration of β-adrenoceptor antagonists upregulate adrenergic system of alveolar macrophage and the potential mechanims. Methods: Propranolol (30 mg/kg·d) or atenolol (5 mg/kg·d) was administered by gavage to rats for 4 weeks. Then alveolar macrophages were isolated and the expression of β 1 or β 2 -adrenoceptor was detected by flow cytometric analysis. Dopamine β-hydroxylase expression was assessed by Western blot assay and the concentrations of noradrenaline, IL-6, and TNF-α in cell supernatants were measured using ELISA after 2 h or 24 h exposure of alveolar macrophages to 100 ng/ml lipopolysaccharide (LPS). Results: Propranolol increased the mean fluorescence intensity (MFI) of β 1 , β 2 -adrenoceptor and the frequency of β 1 -,β 2 -adrenoceptor positive macrophages. However, only the MFI of β 1 -adrenoceptor and the frequency of β 1 -adrenoceptor positive macrophages were increased by atenolol. Furthermore, both propranolol and atenolol promoted LPS-mediated dopamine β-hydroxylase protein expression and increased noradrenaline production in rat alveolar macrophages. This was accompanied by increased LPS-mediated IL-6 and TNF-α production in cell supernatants of alveolar macrophages. Conclusion: These findings demonstrate that propranolol or atenolol upregulates alveolar macrophage adrenergic system, and the response may be β 1 -adrenergic receptor subtype dependent.

Lifelong treatment with atenolol decreases membrane fatty acid unsaturation and oxidative stress in heart and skeletal muscle mitochondria and improves immunity and behavior, without changing mice longevity

“…These age-related decreases were prevented by atenolol in Old-AT mice. Atenolol increases various activities of immune cells in vitro (Guo et al ., 2011 ), but this had not been described previously in vivo .…”

Non-traditional cytokines: How catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system

“…Inhibition of the β-adrenergic receptor with the β-blocker propranolol, or depletion of adrenal catecholamines by adrenalectomy, led to increased LPS-induced tumor necrosis factor (TNF) α production in peritoneal macrophages [12]. Alveolar macrophages recovered from mice chronically treated with β-blockers produced more noradrenaline, interleukin (IL) 6 and TNFα following LPS treatment ex vivo [13]. Conversely, adrenaline, noradrenaline and dopamine treatment of RAW 264.7 macrophages inhibited LPS-induced production of nitric oxide [14].…”

β1‐adrenergic receptor autoantibodies from heart failure patients enhanced TNF‐α secretion in RAW264.7 macrophages in a largely PKA‐dependent fashion

“…They proposed that b 1 -AA mediates catecholamine-like actions leading to the beating rate in spontaneously beating neonatal rat cardiomyocytes [Jane-wit et al, 2007]. It has been reported that catecholamines can either activate [Guo et al, 2011;Nguyen et al, 2011] or suppress [Hasko et al, 1998;Zinyama et al, 2001] macrophage functions, such as the secretion of cytokines. Furthermore, published papers demonstrated that b 1 -adrenergic receptor (b 1 -AR) is expressed on the surface of RAW264.7 cells [Sun et al, 2005].…”