Modulation of superoxide production of alveolar macrophages and peripheral blood mononuclear cells by beta-agonists and theophylline.
Reactive oxygen species, including superoxide anion, have attracted increasing attention for their possible role in promoting inflammation in a variety of pulmonary diseases including asthma. However, reactive oxygen species metabolism of phagocytic cells may be substantially modified by therapeutic agents used for asthma. Peripheral blood mononuclear cells and alveolar macrophages from 15 normal subjects, and blood mononuclear cells from an additional 17 normal subjects, were studied to assess the effects of beta-receptor agonists and theophylline on phagocytic cell superoxide release. Isoproterenol produced a biphasic effect on spontaneous and phorbol ester stimulated alveolar macrophage and mononuclear cell superoxide production, augmenting release at 10(-5)M, and inhibiting release at 10(-4)M. These effects on spontaneous function in mononuclear cells were inhibited by 10(-5)M propranolol. Under conditions of phorbol ester-stimulation the enhancing effect of 10(-5)M isoproterenol on blood mononuclear cells was blocked by propranolol, but the inhibitory effect of 10(-4)M isoproterenol was not. Albuterol at equimolar concentrations with isoproterenol was not associated with altered spontaneous or stimulated superoxide release by alveolar macrophages or mononuclear cells. Further, spontaneous superoxide release by alveolar macrophages and mononuclear cells was significantly reduced by therapeutically achievable concentrations of theophylline (greater than 5 micrograms/ml). We conclude that the medication history must be controlled in studies of cell function in asthma, and that albuterol may be preferable to isoproterenol as a premedication for bronchoscopy when superoxide production of airspace cells is studied.
Section of Pulmonary and Critical Care Medicine, University of Wisconsin, Madison.
W J
WJ
Calhoun
C A
CA
Stevens
S B
SB
Lambert
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D013481:Superoxides; D011433:Propranolol; D013806:Theophylline; D007545:Isoproterenol; D000420:Albuterol