Effect of cyclic adenosine 3',5'-monophosphate antagonists on endotoxin-induced inhibition of human neutrophil chemotaxis.
We reported previously that Escherichia coli endotoxin inhibited human neutrophil chemotaxis toward C5a. This effect of endotoxin was antagonized by anti-inflammatory steroids. We now report that dibutyryl cyclic adenosine 3',5'-monophosphate, prostaglandin E1, isoproterenol, and cholera toxin also antagonize the suppression of chemotaxis by endotoxin. Each compound inhibited the effect of endotoxin in a dose-dependent fashion. To be effective, each compound except cholera toxin had to be present at the time of endotoxin challenge. Furthermore, propranolol blocked the protective effect of isoproterenol against endotoxin but not the protective effect of dibutyrl cyclic adenosine 3',5'-monophosphate or prostaglandin E1. Dibutyryl cyclic guanosine 3',5'-monophosphate, adenosine 5'-monophosphate, phenylephrine, prostaglandin F2 alpha, and carbachol did not modify the suppression of chemotaxis by endotoxin. Anti-inflammatory steroids and dibutyryl cyclic adenosine 3',5'-monophosphate are thought to stabilize phospholipids in certain cell membranes. This phospholipid-stabilizing action may contribute, at least in part, to the protective effect against endotoxin-mediated suppression of neutrophil chemotaxis.
D003994:Bucladesine / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002772:Cholera Toxin / Q000494:pharmacology; D003182:Complement C5 / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism*; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011458:Prostaglandins E / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D003182:Complement C5; D004731:Endotoxins; D011458:Prostaglandins E; D003994:Bucladesine; D002772:Cholera Toxin; D013806:Theophylline; D000242:Cyclic AMP; D007545:Isoproterenol