Modulation of arachidonic acid metabolism and cyclic AMP content of human alveolar macrophages.
The exposure of human alveolar macrophages to inflammatory mediators such as PAF (1 microM), fMLP (1 microM) or the calcium ionophore A23187 (1 microM) induced a rapid decrease in their intracellular concentration of cAMP. Inhibition of TXA2 synthesis by the specific thromboxane synthase inhibitor ridogrel (1-10 microM) or by non-specific inhibitors as indomethacin (1-10 microM), the cyclooxygenase inhibitor, or BW A4C (1-10 microM), the 5-lipoxygenase inhibitor, partially prevented the decrease in cAMP induced by the different inflammatory stimuli. Evidence for an indirect control of cAMP levels in human alveolar macrophages by inflammatory mediators through the production of arachidonic acid derivatives from the cyclooxygenase pathway is supported by this study.
Bachelet
M
M
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur/INSERM 285, Paris, France.
Chouaid
C
C
Havet
N
N
Masliah
J
J
Barre
A
A
Housset
B
B
Vargaftig
B B
BB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016718:Arachidonic Acid / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002452:Cell Count; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic; D016718:Arachidonic Acid; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP