title: Thromboxane-mediated hypertension and vascular leakage evoked by low doses of Escherichia coli hemolysin in rabbit lungs.
abstract: Escherichia coli hemolysin has been implicated as a pathogenicity factor in extraintestinal E. coli infections including sepsis. In the present study the effects of intravascular administration of hemolysin were investigated in isolated blood-free perfused rabbit lungs. Low concentrations of the toxin in the perfusate (0.05-5 hemolytic units/ml, corresponding to approximately 5-500 ng/ml), caused a dose- and time-dependent release of potassium, thromboxane A2, and prostaglandin I2, but not of lactate dehydrogenase, into the recirculating medium, as well as a dose-dependent liberation of the prostanoids into the bronchoalveolar space. These events were paralleled by a dose-dependent pulmonary hypertension, and studies with different inhibitors collectively indicated that the vasoconstrictor response was mediated predominantly by pulmonary thromboxane generation. In addition, E. coli hemolysin elicited a protracted, dose-dependent increase in the lung capillary filtration coefficient, which was independent of the prostanoid-mediated pressor response and resulted in severe pulmonary edema formation. We conclude that E. coli hemolysin can elicit thromboxane-mediated pulmonary hypertension combined with severe vascular leakage in isolated lungs in the absence of circulating inflammatory cells and humoral mediator systems, mimicking the key events in the development of acute respiratory failure in states of septicemia.
authors.affiliation: Department of Internal Medicine, Justus-Liebig-University Giessen, Federal Republic of Germany.
authors.forename: W
authors.initials: W
authors.lastname: Seeger
authors.forename: H
authors.initials: H
authors.lastname: Walter
authors.forename: N
authors.initials: N
authors.lastname: Suttorp
authors.forename: M
authors.initials: M
authors.lastname: Muhly
authors.forename: S
authors.initials: S
authors.lastname: Bhakdi
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors; D002118:Calcium / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D011464:Epoprostenol / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000150:complications; D006460:Hemolysin Proteins / Q000633:toxicity*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism*; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D009929:Organ Size; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012131:Respiratory Insufficiency / Q000209:etiology; D013928:Thromboxane A2 / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D006460:Hemolysin Proteins; D013928:Thromboxane A2; D011464:Epoprostenol; D011188:Potassium; D002118:Calcium