Regulation of the respiratory burst by cyclic 3',5'-AMP, an association with inhibition of arachidonic acid release.
The mechanism of cAMP regulation of the respiratory burst was studied with HL-60 cells that had been DMSO-differentiated to a neutrophil-like cell. To evaluate the effects of known cAMP concentrations, cells were permeabilized with streptolysin-O. Chemotactic peptide (FMLP)-stimulated NADPH oxidase activity was inhibited by cAMP at concentrations higher than 3 microM. Because intracellular calcium was buffered, inhibitory actions of cAMP were not mediated by modulation of calcium concentration. Effects of cAMP on chemotactic peptide signal transduction mediated by phospholipase C, phospholipase D, and phospholipase A2 were then determined. Neither inositol phosphate generation (phospholipase C) nor phosphatidylethanol generation (phospholipase D activity in presence of 1.6% ethanol) induced by FMLP were significantly affected by cAMP. In contrast, cAMP potently inhibited FMLP-induced arachidonic acid mobilization (phospholipase A2). NADPH oxidase activity induced by exogenous arachidonic acid was not inhibited by cAMP. These results indicate that cAMP-mediated inhibition of arachidonic acid mobilization may be important in regulation of the respiratory burst.
Nielson
C P
CP
Clinical Pharmacology and Gerontology Research Unit, Veterans Affairs Medical Center, Boise, ID 83702.
Bayer
C
C
Hodson
S
S
Hadjokas
N
N
D000166:Acridines / Q000378:metabolism; D000704:Analysis of Variance; D016718:Arachidonic Acid / Q000096:biosynthesis*; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D005786:Gene Expression Regulation; D020404:Glycerophospholipids; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010739:Phospholipase D; D010741:Phospholipases A; D054467:Phospholipases A2; D016897:Respiratory Burst / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases
D000166:Acridines; D020404:Glycerophospholipids; D007295:Inositol Phosphates; D010712:Phosphatidic Acids; C051521:phosphatidylethanol; C033472:10,10'-dimethyl-9,9'-biacridinium; D016718:Arachidonic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D010739:Phospholipase D