Human alveolar macrophage activation: inhibition by forskolin but not beta-adrenoceptor stimulation or phosphodiesterase inhibition.
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.
Fuller
R W
RW
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
O'Malley
G
G
Baker
A J
AJ
MacDermot
J
J
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*
D000318:Adrenergic beta-Agonists; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin