Analysis of granulocyte beta-adrenergic response in cystic fibrosis: correlation of decreased responsiveness with disease severity.
Granulocytes from 21 nonasthmatic cystic fibrosis (CF) patients were isolated and the effects of isoproterenol, histamine, and prostaglandin E1 upon zymosan-induced beta-glucuronidase release was measured. Granulocytes from CF patients contained significantly less total beta-glucuronidase activity compared with those from control subjects, but response to zymosan stimulation was normal. Compared with those from control subjects, the granulocytes from CF patients with severe airway disease (% predicted FEV1 less than 60) had significantly reduced responsiveness to isoproterenol, which correlated with both the % predicted FEV1 values and the NIH clinical score. In this same population of CF patients, granulocyte responsiveness to PGE1 was also decreased compared with that of the control subjects, but the degree of impairment was not as severe as that observed with isoproterenol nor did it correlate with disease severity. Histamine responsiveness, however, was normal. Our findings suggest that abnormal beta-adrenergic responses may reflect the severity of airway disease and clinical score.
D000293:Adolescent; D000402:Airway Obstruction / Q000097:blood / Q000201:enzymology / Q000503:physiopathology; D002648:Child; D003550:Cystic Fibrosis / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D005966:Glucuronidase / Q000378:metabolism*; D006098:Granulocytes / Q000187:drug effects* / Q000201:enzymology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D011458:Prostaglandins E / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D011458:Prostaglandins E; D006632:Histamine; D015054:Zymosan; D005966:Glucuronidase; D007545:Isoproterenol