Pasteurella haemolytica lipopolysaccharide-induced cytotoxicity in bovine pulmonary artery endothelial monolayers: inhibition by indomethacin.
Exposure of bovine pulmonary artery endothelial cells to Pasteurella haemolytica lipopolysaccharide caused severe morphologic changes. Initially, there was dilatation of the rough endoplasmic reticulum and mitochondrial swelling followed by cell retraction, membrane bleb formation, and cell detachment. The affected endothelial cells had severe membrane damage resulting in the leakage of lactate dehydrogenase. Indomethacin in concentrations of 0.5 mM or greater caused marked decreases in the lipopolysaccharide-induced leakage of lactate dehydrogenase. Indomethacin at 5 mM also caused a marked reduction of the lipopolysaccharide-induced morphologic changes resulting in apparent maintenance of the monolayer integrity for 8 hours versus 1 hour in the lipopolysaccharide-treated control. A marked decrease in the cell and nuclear membrane effects resulted, but the rough endoplasmic reticulum dilatation and mitochondrial changes proceeded. These results indicate that indomethacin does not prevent lipopolysaccharide binding but interferes with later events in lipopolysaccharide-induced cytotoxicity in the bovine pulmonary endothelial cell. The concentration of indomethacin required to produce this inhibition suggests that the primary mechanism is not cyclooxygenase inhibition.
Paulsen
D B
DB
Department of Veterinary Pathology, College of Veterinary Medicine, Oklahoma State University, Stillwater, USA.
Confer
A W
AW
Clinkenbeard
K D
KD
Mosier
D A
DA
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D016978:Mannheimia haemolytica / Q000737:chemistry*; D008854:Microscopy, Electron / Q000662:veterinary; D008855:Microscopy, Electron, Scanning / Q000662:veterinary; D010865:Pilot Projects; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D008070:Lipopolysaccharides; D007770:L-Lactate Dehydrogenase; D007213:Indomethacin