Dual effects of Haemophilus influenzae on guinea pig tracheal beta-adrenergic receptor function: involvement of oxygen-centered radicals from pulmonary macrophages.
The Gram-negative bacterium Haemophilus influenzae has been shown to cause a deterioration of the guinea pig pulmonary beta-adrenergic receptor system. In the present study we investigated further the mechanisms behind this effect. To this extent we evaluated the involvement of pulmonary macrophages (PM). Treatment of guinea pigs with killed H. influenzae bacteria resulted in the accumulation of a factor in the serum which could specifically stimulate PM. Thus stimulated, PM from nontreated animals caused a decrease of tracheal beta-adrenergic receptor function in vitro. This effect was evident by a decrease of the maximal response of the dose-response curves to isoprenaline, whereas the EC50 values did not change. Catalase and thiourea abolished the PM-induced effects, whereas superoxide dismutase did not, indicating that oxygen-centered radicals, in particular the highly reactive hydroxyl radical, may be responsible for the observed effects. In addition, dexamethasone also inhibited the decrease of tracheal beta-adrenergic receptor function. When activated PM, taken from animals that had been pretreated with killed H. influenzae bacteria 4 days beforehand, were stimulated with serum from a H. influenzae-treated animal, a potentiation of tracheal beta-adrenergic receptor function was observed.
D000818:Animals; D005609:Free Radicals; D006168:Guinea Pigs; D006193:Haemophilus influenzae / Q000502:physiology*; D006878:Hydroxides; D017665:Hydroxyl Radical; D007545:Isoproterenol / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000166:cytology*; D014132:Trachea / Q000378:metabolism* / Q000382:microbiology
D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D007545:Isoproterenol