Infectious-inflammatory changes in cyclic AMP levels and in their regulation by prostaglandins in human peritoneal macrophages.
Peritoneal macrophages of renal patients on continuous ambulatory peritoneal dialysis (CAPD) have been collected when CAPD was without complications, during an intercurrent infectious peritoneal inflammation and after recovery. Levels of cyclic AMP, release of cyclo-oxygenase metabolites, and responsiveness, in terms of cyclic AMP elevation, to either PGE2 or to DC-PGI2 (a stable analogue of PGI2) were examined. Peritoneal inflammation was associated with a sharp drop in cyclic AMP, which was restored after recovery. Production of TXA2, PGI2 and PGE2 parallelled the direction of changes in cyclic AMP levels, except, that release of PGE2 entirely failed to recover. Macrophages during the uncomplicated stage of CAPD proved more responsive to DC-PGI2 than to PGE2. During inflammation the cells displayed a marked increase in sensitivity towards PG stimulation. Improved sensitivity was more pronounced with PGE2 than with DC-PGI2 and so the original difference between responsiveness of the cells to the PGs was abolished. Several findings are compatible with the view that endogenous PGI2 governs the cyclic AMP levels in human non-inflammatory peritoneal macrophages. However, during infectious-inflammation the cells undergo changes which render a reduced production of PGI2 insufficient to explain the drop in cyclic AMP.
Adolfs
M J
MJ
Fieren
M W
MW
Bonta
I L
IL
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000328:Adult; D000368:Aged; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone; D011464:Epoprostenol / Q000494:pharmacology / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010538:Peritonitis / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism
D011458:Prostaglandins E; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C039191:FCE 21258; D011464:Epoprostenol; D000242:Cyclic AMP; D015232:Dinoprostone