Bacterial toxin-induced pulmonary epithelial cytotoxicity and the protective effect of dibutyryl-cAMP.
Bacterial infection is the most common cause of the adult respiratory distress syndrome which, in turn is associated with endothelial capillary permeability and alveolar oedema. Previously, we have demonstrated the direct cytotoxicity of the bacterial toxins Pseudomonas aeruginosa exotoxin A (Exo A) and Salmonella enteritidis lipopolysaccharide (LPS) on pulmonary endothelial cells. The purpose of this study was to investigate the effect of Exo A and LPS on pulmonary epithelial cells in vitro. We also tested the protective effect of dibutyryl cyclic adenosine monophosphate (db-cAMP) on Exo A-induced cytotoxicity. In cultured rat alveolar epithelial cells (RAEC) Exo A caused cytotoxicity as measured by 51Cr release from these cells. LPS did not injure RAEC's. Pretreatment of RAEC with db-cAMP (1 mM) attenuated Exo A induced cytotoxicity. We conclude that (1) Exo A directly injures epithelial lung cells and may contribute to lung injury in cases of bacterial infection; (2) db-cAMP protects alveolar epithelial cells against Exo A-induced cytotoxicity and (3) alveolar epithelial cells in this model are resistant to LPS induced injury.
Bourke
W
W
Department of Medicine, Northwestern University Medical School, Chicago, IL, USA.
Kamp
D
D
Dunn
M
M
Chang
S W
SW
D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005098:Exotoxins / Q000633:toxicity; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology; D012477:Salmonella enteritidis; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D003994:Bucladesine; D005098:Exotoxins; D008070:Lipopolysaccharides; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A