Effect of cyclic adenosine monophosphate elevations on functional responses of polymorphonuclear leukocytes from patients with cystic fibrosis.
Recently, it has been suggested that the primary metabolic defect of cystic fibrosis (CF) is in the metabolic steps between an elevation of cyclic adenosine monophosphate (cAMP) and the opening of the Cl- ion channel in airway epithelial cells. Results from other studies have indicated that the primary defect may also be present in polymorphonuclear leukocytes (PMNL). In PMNL, cAMP is a potent inhibitor of cell function. We therefore used three compounds (epinephrine, theophylline, and forskolin) known to elevate cAMP in PMNL by three different mechanisms, to study the effect of an elevation of cAMP on various cell functions, such as superoxide production, membrane depolarization, and degranulation of CF patient PMNL and PMNL from healthy individuals. The baseline rates of superoxide production, degranulation, and membrane depolarization were identical for CF and control PMNL. After exposure to epinephrine as well as theophylline plus forskolin, the cell function of CF PMNL was inhibited to the same extent as that of control PMNL. Our results argue against an abnormal response of PMNL from patients with CF to an elevation of cAMP.
Suter
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S
Department of Pediatrics, University of Geneva, Switzerland.
Chevallier
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Krause
K H
KH
Lew
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DP
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism / Q000503:physiopathology*; D003594:Cytoplasmic Granules / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials; D009504:Neutrophils / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology
D013481:Superoxides; D005576:Colforsin; D013806:Theophylline; D000242:Cyclic AMP; D004837:Epinephrine