Function of β2-adrenoceptors on alveolar macrophages

β2-agonists are very effective drugs for bronchodilatation, provide a rapid relief of symptoms in asthma, and are recommended as first line treatment, together with steroids. The relaxation of bronchial smooth muscles is a well-established effect of β-agonists, but their effects on inflammatory cells in the airways are less certain. Alveolar macrophages are easily harvested by bronchoalveolar lavage and are the most numerous cell in lavage fluid. Our investigations were all performed on human alveolar macrophages.

β-adrenoceptors on alveolar macrophages were characterized by studying cAMP accumulation in intact macrophages evoked by adrenaline or isoprenaline, with or without appropriate antagonists, as well as by radioligand binding to macrophage membrane, using [125]-iodopindololas β-adrenoceptor ligand. We could conclude that alveolar macrophages are endowed with functional β-adrenoceptors and these receptors are of β2-adrenoceptor subtype.

Possible desensitization of β2-adrenoceptors on alveolar macrophages upon agonist stimulation were investigated in healthy volunteers, treated during two weeks with terbutaline, orally or by the inhaled route. Bronchoalveolar lavage was performed before and after the treatment period. Possible steroid effects were studied with inhalation of budesonide throughout the treatment period or by 40 mg prednisolone before the second bronchoalveolar lavage in a placebo controlled manner. There was a marked desensitization of alveolar macrophage β2-adrenoceptors, and the desensitization was of the same magnitude if terbutaline was inhaled or taken orally. This desensitization was not prevented by inhaled steroid, or reversed by oral treatment with corticosteroid before the second investigation.

The influence of β2-agonists and a corticosteroid on the secretion of interleukin-1β and leukotriene β4 from alveolar macrophages and blood monocytes were investigate. Cells from healthy volunteers were incubated with two short- and two long-acting, β-agonists and with budesonide. Budesonide decreased the secretion of interleukin-1β from monocytes. None of the drugs influenced the secretions of interleukin-1β or leukotriene B4 from alveolar macrophages.

Alveolar macrophages were incubated with terbutaline or budesonide and phagocytic capacity of FITC-labelled E.coli was assessed by flow cytometry. Budesonide, but not terbutaline decreased the phagocytosis in a dose dependent way.

In conclusion, these studies show that treatment with common anti-asthma drugs markedly affect the functional characteristics for one of the most important pulmonary cells, the alveolar macrophage.