title: Human alveolar macrophage activation: inhibition by forskolin but not beta-adrenoceptor stimulation or phosphodiesterase inhibition.
abstract: Alveolar macrophages are the most numerous cells within human airways. They release inflammatory mediators following immunological challenge and have been implicated in the pathogenesis of asthma. beta-agonists and phosphodiesterase inhibitors are frequently used in the treatment of asthma and are potent inhibitors of human mast cells. We have examined the role of the beta-agonist, isoprenaline, the phosphodiesterase inhibitor Ro-20 1724, and the adenylate cyclase stimulator forskolin on the activation of human alveolar macrophages. This was assessed by monitoring the release of thromboxane B2 (TXB2), leukotriene B4, N-acetyl-beta-D-glucosaminidase (NAG), and superoxide (SO) following stimulation of the cells by opsonised zymosan or IgE/anti IgE complexes. Neither isoprenaline (1nM-10 microM) nor Ro-20 1724 (0.5-50 microM) alone or in combination had any inhibitory effect on release of these mediators. However, forskolin (0.1-100 microM) significantly inhibited release of both TXB2 and SO but not NAG. This result shows that human alveolar macrophages do not possess functional beta-receptors, although stimulation of adenylate cyclase with forskolin, inhibits some of the elements of macrophage activation.
authors.affiliation: Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
authors.forename: R W
authors.initials: RW
authors.lastname: Fuller
authors.forename: G
authors.initials: G
authors.lastname: O'Malley
authors.forename: A J
authors.initials: AJ
authors.lastname: Baker
authors.forename: J
authors.initials: J
authors.lastname: MacDermot
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin