Inflammatory lipid mediator generation elicited by viable hemolysin-forming Escherichia coli in lung vasculature.
Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor for E. coli-related extraintestinal infections and sepsis. The possible significance of hemolysin liberation for induction of inflammatory lipid mediators was investigated in isolated rabbit lungs infused with viable bacteria (concentration range, 10(4)-10(7)/ml). Hemolysin-secreting E. coli (E. coli-Hly+), but not an E. coli strain that releases an inactive form of the exotoxin, induced marked lung leukotriene (LT) generation with predominance of cysteinyl LTs. Eicosanoid synthesis was not inhibited in the presence of plasma with toxin-neutralizing capacity. Pre-application of 2 x 10(8) human granulocytes, which sequestered in the lung microvasculature, caused a severalfold increase in leukotriene generation in response to E. coli-Hly+ challenge both in the absence and presence of plasma. Data are presented indicating neutrophil-endothelial cell cooperation in arachidonic acid lipoxygenase metabolism as an underlying mechanism. We conclude that liberation of hemolysin from viable E. coli induces marked lipid mediator generation in lung vasculature, which is potentiated in the presence of neutrophil sequestration and may contribute to microcirculatory disturbances during the course of severe infections.
Grimminger
F
F
Department of Internal Medicine, Justus-Liebig-University, Giessen, Federal Republic of Germany.
Thomas
M
M
Obernitz
R
R
Walmrath
D
D
Bhakdi
S
S
Seeger
W
W
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D004926:Escherichia coli / Q000472:pathogenicity*; D005260:Female; D006460:Hemolysin Proteins / Q000633:toxicity*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D010477:Perfusion; D011817:Rabbits
D001095:Arachidonic Acids; D006460:Hemolysin Proteins; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid