Different sensitivity of Pseudomonas aeruginosa exotoxin A and diphtheria toxin to enzymes from polymorphonuclear leukocytes.
We demonstrate that exotoxin A (ExoA) of Pseudomonas aeruginosa is one to two orders of magnitude more sensitive than diphtheria toxin (DT) of Corynebacterium diphtheriae to lysosomal enzymes from polymorphonuclear leukocytes (PMN). It is especially sensitive to PMN elastase which inactivates its cell free enzymatic activity and its cytotoxicity as measured with the Chinese hamster ovary cell assay and the rabbit skin test. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) showed a rapid fragmentation of ExoA into small peptides at low PMN elastase concentrations, whereas DT remained largely uncleaved at PMN elastase concentrations 10 times higher. PMN elastase also removed the cell surface receptors for ExoA and DT on Chinese hamster ovary cells, suggesting that both toxins may be ineffective at local sites of severe inflammation. A comparison of fibroblasts from cystic fibrosis patients and normal healthy individuals revealed no differences in susceptibility to either DT or ExoA; this tends to exclude a genetic defect as an explanation for the absence of ExoA effects in cystic fibrosis patients.
Döring
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Hygiene-Institute, University of Tübingen, F.R.G.
Müller
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E
D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins; D002352:Carrier Proteins; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000276:immunology; D004167:Diphtheria Toxin / Q000378:metabolism*; D005098:Exotoxins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic / Q000378:metabolism; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D002352:Carrier Proteins; D004167:Diphtheria Toxin; D005098:Exotoxins; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D010196:Pancreatic Elastase; D011065:Poly(ADP-ribose) Polymerases; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; C027553:Pseudomonas exotoxin binding protein, mouse