Bacterial exotoxins and endothelial permeability for water and albumin in vitro.
Effects of Staphylococcus aureus alpha-toxin and Pseudomonas aeruginosa cytotoxin on the permeability of an endothelial monolayer were studied. Porcine pulmonary artery endothelial cells were grown on a polycarbonate membrane, mounted in a chamber, and exposed to a continuous hydrostatic pressure of 10 cmH2O. On application of this trans-endothelial pressure, endothelial monolayer became "sealed," i.e., the filtration rate for water decreased and the reflection coefficient for albumin increased, reaching a plateau after 1-2 h. Sealed monolayer had a hydraulic conductivity of 2.1 X 10(-6) cm.s-1.cmH2O and an albumin reflection coefficient of 0.73. Permeability of the monolayer was increased on addition of an excess of EDTA and reversed on readdition of calcium. Within 60-90 min after addition of 1 microgram/ml alpha-toxin, the filtration rate increased 75-fold, and the albumin reflection coefficient dropped to 0.20. These changes in permeability were accompanied by cell retraction and formation of large intercellular gaps between endothelial cells. Effects of alpha-toxin were abolished by preincubation with neutralizing antibodies and by inhibitors of calmodulin function. Pseudomonas aeruginosa cytotoxin (25 and 50 micrograms/ml) also increased the permeability of the endothelial monolayer, but it was only about one-third as effective as alpha-toxin.
D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D005098:Exotoxins / Q000494:pharmacology*; D006460:Hemolysin Proteins; D008855:Microscopy, Electron, Scanning; D011550:Pseudomonas aeruginosa; D011651:Pulmonary Artery / Q000502:physiology; D012709:Serum Albumin / Q000378:metabolism*; D013211:Staphylococcus aureus; D013552:Swine; D037521:Virulence Factors; D014867:Water; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D012709:Serum Albumin; D037521:Virulence Factors; D014867:Water; D000097668:Pseudomonas aeruginosa Exotoxin A; C021091:staphylococcal alpha-toxin