title: Lung vascular injury after administration of viable hemolysin-forming Escherichia coli in isolated rabbit lungs.
abstract: Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor. In the present study, the possible significance of hemolysin production was investigated in a model of septic lung failure through infusion of viable bacteria in isolated rabbit lungs; 10(4) to 10(7) E. coli/ml perfusate caused a dose- and time-dependent appearance of hemolysin, accompanied by release of potassium, thromboxane A2, and PGI2 into the perfusate. Concomitantly, marked pulmonary hypertension developed. Inhibitor studies suggested that the pressor response was predominantly mediated by pulmonary thromboxane generation. Administration of hemolysin-forming E. coli additionally caused a protracted, dose-dependent increase in the lung capillary filtration coefficient, followed by severe edema formation. The permeability increase was independent of lung prostanoid generation. An E. coli strain that releases an inactive form of hemolysin completely failed to provoke the described biophysical and biochemical responses. Preapplication of 2 x 10(8) human granulocytes was without effect in the present experimental model. We conclude that the hemolysin produced by low numbers of E. coli organisms can provoke thromboxane-mediated pulmonary hypertension and severe vascular leakage. E. coli hemolysin and, possibly, other related cytolysins may thus contribute directly to the pathogenesis of acute respiratory failure under conditions of sepsis or pneumonia.
authors.affiliation: Department of Internal Medicine, Justus-Liebig University, Giessen, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Seeger
authors.forename: R
authors.initials: R
authors.lastname: Obernitz
authors.forename: M
authors.initials: M
authors.lastname: Thomas
authors.forename: D
authors.initials: D
authors.lastname: Walmrath
authors.forename: N
authors.initials: N
authors.lastname: Suttorn
authors.forename: I B
authors.initials: IB
authors.lastname: Holland
authors.forename: F
authors.initials: F
authors.lastname: Grimminger
authors.forename: B
authors.initials: B
authors.lastname: Eberspächer
authors.forename: F
authors.initials: F
authors.lastname: Hugo
authors.forename: S
authors.initials: S
authors.lastname: Bhakdi
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure; D002199:Capillary Permeability; D011464:Epoprostenol / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity*; D005260:Female; D006460:Hemolysin Proteins / Q000096:biosynthesis / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000382:microbiology / Q000503:physiopathology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D009504:Neutrophils / Q000502:physiology; D010477:Perfusion; D011188:Potassium / Q000378:metabolism; D011651:Pulmonary Artery / Q000502:physiology; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane; D012131:Respiratory Insufficiency / Q000382:microbiology / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism
chemical_list: D006460:Hemolysin Proteins; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C040624:sulotroban; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D001241:Aspirin; D011188:Potassium