Endothelial Exposure to Pseudomonas aeruginosa Proteases Increases the Vulnerability of the Alveolar Epithelium to a Second Injury

Abstract

The alveolar epithelium is not injured by the apical application of moderate doses of Pseudomonas aeruginosa strains that produce protease. To determine the effect of Pseudomonas proteases on the basolateral surface of the alveolar epithelium, a series of experiments were done, in which P. aeruginosa strains that produce and do not produce proteases were administered intravenously. Subsequently, an innocuous dose of bacteria was instilled into the lungs of the rabbits. Although all the intravenous Pseudomonas strains increased the extravascular lung water to a similar degree, only the intravenous administration of the protease-producing P. aeruginosa strain increased the vulnerability of the alveolar epithelium to injury by the subsequent airspace bacteria. Bacteremia secondary to P. aeruginosa strains producing proteases could increase the chances of developing acute lung injury.

Intravenous administration of activated protein C in Pseudomonas-induced lung injury: impact on lung fluid balance and the inflammatory response

“…In this hypothesis, the worsening of the oxygenation was not related to alveolar flooding but to mismatched of V/Q. Our findings are consistent with previous results of others indicating that alveolar epithelium is more resistant than the lung endothelium to acute lung injury [ 31 - 33 ]. We have also previously shown in another model that this discrepancy between ALC and LLC could be related to the endothelial barrier [ 34 ].…”

“…The following parameters were measured 4 hours post-instillation of bacteria in blood samples obtained through direct aortic catheterization of anesthetized rats from each group: leukocyte and platelet counts, prothrombin time, fibrinogen and thrombin-antithrombin (TAT) complex concentrations. Measurements of TAT complexes were used as markers of thrombin formation [ 33 ]. TAT complexes were also measured in BAL fluids.…”

Role of Small GTPases and αvβ5 Integrin in Pseudomonas aeruginosa–Induced Increase in Lung Endothelial Permeability

“…In particular, we have shown that a large amount of the P. aeruginosa bacteria instilled into the distal airspaces go through the distal lung epithelium come in contact with the lung endothelium before reaching the bloodstream and cause the development of pulmonary edema (41). We have also reported that the intravenous administration of P. aeruginosa resulted in an increase of the vulnerability of the alveolar capillary barrier to an exposure to a nontoxic inoculum of the same bacterium instilled into the distal airspace of the lung (40). This previously published study demonstrated how P. aeruginosa in the circulation could amplify the minor lung epithelial injury caused by bacteria that colonize the distal airways.…”

“…Briefly, the endothelial cells were grown on 35-mm cell culture dishes to 50% 6,40) confluence. After serum starvation for 6 hours, the wild-type P. aeruginosa strain PAK (bacterial to bovine cell ratio: Endothelial cells were grown on collagen-coated glass coverslips to confluence.…”

“…Further, the integrity of the two cellular barriers affect each other (40). We have previously investigated the damaging effect of P. aeruginosa on the distal lung epithelium.…”