Pseudomonas aeruginosa exotoxin A induces pulmonary endothelial cytotoxicity: protection by dibutyryl-cAMP.
In pseudomonal septicaemia, serum levels of antibody to exotoxin A have been demonstrated to be an important independent predictor of survival. Previously, we have demonstrated that exotoxin A directly injures pulmonary endothelial cells, and that dibutyryl-cyclic adenosine monophosphate (Db-cAMP) can attenuate this injury. The object of this study was to examine the mechanisms of this pulmonary endothelial cell injury and the mechanism of Db-cAMP protection. The effects of differing duration of exposure to exotoxin A and a reduction in temperature on endothelial cell injury were examined. In addition, the effect of post-treatment with Db-cAMP on exotoxin A-induced endothelial cell injury was studied. A brief, 5 min, exposure to exotoxin resulted in maximum injury comparable to that produced by 18 h exposure. This injury did not occur at low temperatures, which would inhibit receptor-mediated endocytosis. Db-cAMP protected endothelial cells, even when added up to one hour after exotoxin exposure. These results suggest that, in this model, exotoxin A-induced injury of endothelial cells is receptor-mediated. Furthermore, this injury may be attenuated even after exotoxin A internalization has taken place.
Bourke
W J
WJ
Dept of Medicine and Therapeutics, University College Dublin, Belfield, Eire.
O'Connor
C M
CM
FitzGerald
M X
MX
McDonnell
T J
TJ
D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D002860:Chromium Radioisotopes; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005098:Exotoxins / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D003994:Bucladesine; D002860:Chromium Radioisotopes; D005098:Exotoxins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A