Pseudomonas aeruginosa exotoxin A induces pulmonary endothelial cytotoxicity: protection by dibutyryl-cAMP

W.J. Bourke, C.M. O'Connor, M.X. FitzGerald, T.J. McDonnell
1994 European Respiratory Journal  
P Ps se eu ud do om mo on na as s a ae er ru ug gi in no os sa a e ex xo ot to ox xi in n A A i in nd du uc ce es s p pu ul lm mo on na ar ry y e en nd do ot th he el li ia al l c cy yt to ot to ox xi ic ci it ty y: : p pr ro ot te ec ct ti io on n b by y d di ib bu ut ty yr ry yl l--c cA AM MP P ABSTRACT: 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
more » ... ated 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.
doi:10.1183/09031936.94.07101754 pmid:7828680 fatcat:i2hdh57ubjhufjqvvxv7tu7nj4