Bactericidal defect of neutrophils in a guinea pig model of thermal injury is related to elevation of intracellular cyclic-3',5'-adenosine monophosphate.
PG of the E series inhibit major effector functions of polymorphonuclear leukocytes (PMN) by elevating intracellular cAMP. The present study investigated the involvement of this mechanism in the bactericidal defect of PMN induced by thermal injury in a guinea pig model. Peripheral and peritoneal exudate PMN harvested from thermally injured guinea pigs at 1 or 2 days postburn had decreased bactericidal activity against Pseudomonas aeruginosa and a marked increase in cAMP content. Production of PGE1 by these cells in the absence of exogenous PMN activators was also increased. Treatment of PMN in vitro or in vivo with nonsteroidal anti-inflammatory drugs (indomethacin, ibuprofen, and piroxicam) restored bactericidal activity to normal and concomitantly reduced cAMP content and PGE1 production. A concomitant reduction in cAMP content and PGE1 production was also observed as bactericidal activity of PMN returned to normal under natural conditions during 4 to 7 days postburn. The enhancement of PMN bactericidal activity mediated by NSAID was fully counteracted by purified PGE1, theophylline, and by cAMP itself. These results suggest that the bactericidal defect of PMN induced by thermal injury is related to elevation of cAMP and that PGE1 plays a significant role in this phenomenon.
Bjornson
A B
AB
Division of Immunology, James N. Gamble Institute of Medical Research, Cincinati, Ohio 45219.
Knippenberg
R W
RW
Bjornson
H S
HS
D000527:Alprostadil / Q000096:biosynthesis / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001202:Ascitic Fluid / Q000382:microbiology; D001770:Blood Bactericidal Activity / Q000187:drug effects; D002056:Burns / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013481:Superoxides / Q000097:blood; D013806:Theophylline / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013481:Superoxides; D013806:Theophylline; D000242:Cyclic AMP; D000527:Alprostadil; D015232:Dinoprostone