Journal article

Publication year: 1994

Pages: 1437-1443

Journal: Journal of Experimental Medicine

Volume number: 180

Issue number: 4

ISSN: 0022-1007

Open access status: Green

DOI Link: https://doi.org/10.1084/jem.180.4.1437

Publisher: Rockefeller University Press

Abstract: 
The pore-forming hemolysin of Escherichia coli (HlyA), an important virulence factor in extraintestinal E. coli infections, causes thromboxane generation and related vasoconstriction in perfused rabbit lungs (Seeger, W., H. Waiter, N. Suttorp, M. Muhly, and S. Bhakdi. 1989. J. Clin. Invest, 84:220). We investigated the influence of pulmonary vascular ''priming'' with endotoxin on the responsiveness of the lung to a low-dose HlyA challenge. Rabbit lungs were perfused with Krebs Henseleit buffer containing 0.1-100 ng/ml Salmonella abortus equii lipopolysaccharide (LPS) for 60-180 min. This treatment caused protracted release of tumor necrosis factor into the recirculating medium, but did not induce significant alterations of pulmonary hemodynamics and fluid balance. At a dose of 1 ng/ml, HlyA elicited only moderate thromboxane release (<200 pg/ml) and pulmonary artery pressure increase (less than or equal to 6 mmHg) in control lungs. Acceleration and potentiation of both the metabolic and vasoconstrictor response occurred in lungs primed with LPS. This priming effect displayed dose (threshold similar to 0.1-1 ng/ml LPS) and time dependencies (threshold similar to 60-90 min LPS incubation). Maximum thromboxane release and pulmonary artery pressure increase surpassed the responses to HlyA in nonprimed lungs by more than 15-fold. Cyclooxygenase inhibition and thromboxane-receptor antagonism blocked these effects. These data demonstrate that LPS priming synergizes with HlyA challenge to provoke vascular abnormalities that are possibly relevant to the pathogenesis of organ failure in severe local and systemic infections.

Harvard Citation style: WALMRATH, D., Ghofrani, H., ROSSEAU, S., SCHUTTE, H., CRAMER, A., KADDUS, W., et al. (1994) ENDOTOXIN PRIMING POTENTIATES LUNG VASCULAR ABNORMALITIES IN RESPONSE TO ESCHERICHIA-COLI HEMOLYSIN - AN EXAMPLE OF SYNERGISM BETWEEN ENDOTOXIN AND EXOTOXIN, Journal of Experimental Medicine, 180(4), pp. 1437-1443. https://doi.org/10.1084/jem.180.4.1437

APA Citation style: WALMRATH, D., Ghofrani, H., ROSSEAU, S., SCHUTTE, H., CRAMER, A., KADDUS, W., Grimminger, F., BHAKDI, S., & Seeger, W. (1994). ENDOTOXIN PRIMING POTENTIATES LUNG VASCULAR ABNORMALITIES IN RESPONSE TO ESCHERICHIA-COLI HEMOLYSIN - AN EXAMPLE OF SYNERGISM BETWEEN ENDOTOXIN AND EXOTOXIN. Journal of Experimental Medicine. 180(4), 1437-1443. https://doi.org/10.1084/jem.180.4.1437