Cyclic AMP enhancing drugs modulate eicosanoid release from human alveolar macrophages.
The effect of the phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX), salbutamol and sodium nitroprusside was evaluated regarding PGE2 and LTB4 release and cAMP and cGMP level in human alveolar macrophages obtained from controls and COPD patients. Basal levels per five million control- respectively COPD alveolar macrophages: cAMP 1.2 and 1.0 pmole; cGMP 8.4 and 9.1 fmole; PGE2 120 and 63 pg and LTB4 19.2 and 14.8 pg. In both populations IBMX increased cAMP level by 55-93% and salbutamol+IBMX by 285-252%. Except for the 61% rise in LTB4 release by salbutamol+IBMX the drugs hardly affected PGE2 and LTB4 release from control macrophages. In COPD alveolar macrophages, however, IBMX and IBMX+salbutamol largely reduced PGE2 release (63 vs 11 pg per 10(6) cells) but less efficiently increased LTB4. In both macrophage populations sodium nitroprusside (SNP) substantially increased (3-4 fold) cGMP level but did not affect eicosanoid production. Present results indicate that drugs which enhance cAMP level decrease PGE2 release from COPD macrophages and stimulate the release of LTB4 a chemotactic mediator involved in bronchial inflammatory reactions.
Beusenberg
F D
FD
Department of Pharmacology, Faculty of Medicine, Erasmus University Rotterdam, The Netherlands.
Hoogsteden
H C
HC
Bonta
I L
IL
van Amsterdam
J G
JG
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D000242:Cyclic AMP / Q000096:biosynthesis*; D006152:Cyclic GMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008168:Lung / Q000473:pathology; D008173:Lung Diseases, Obstructive / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D012907:Smoking / Q000473:pathology
D009599:Nitroprusside; D007975:Leukotriene B4; D000242:Cyclic AMP; D006152:Cyclic GMP; D015232:Dinoprostone; D000420:Albuterol; D015056:1-Methyl-3-isobutylxanthine