Bβ15–42 Protects against Acid-induced Acute Lung Injury and Secondary Pseudomonas Pneumonia In Vivo
U Matt, JM Warszawska, M Bauer, W Dietl… - American journal of …, 2009 - atsjournals.org
U Matt, JM Warszawska, M Bauer, W Dietl, I Mesteri, B Doninger, I Haslinger, G Schabbauer…
American journal of respiratory and critical care medicine, 2009•atsjournals.orgRationale: Acute lung injury (ALI) is a serious condition in critically ill patients that
predisposes to secondary bacterial pneumonia. Vascular leak is a hallmark in the
pathogenesis of ALI. The fibrin-derived peptide Bβ15–42 was shown to preserve endothelial
barriers, thereby reducing vascular leak. The potential therapeutic role of Bβ15–42 in ALI
has not been addressed so far. Objectives: To investigate the therapeutic potential of Bβ15–
42 in ALI and secondary pneumonia induced by Pseudomonas aeruginosa. Methods: The …
predisposes to secondary bacterial pneumonia. Vascular leak is a hallmark in the
pathogenesis of ALI. The fibrin-derived peptide Bβ15–42 was shown to preserve endothelial
barriers, thereby reducing vascular leak. The potential therapeutic role of Bβ15–42 in ALI
has not been addressed so far. Objectives: To investigate the therapeutic potential of Bβ15–
42 in ALI and secondary pneumonia induced by Pseudomonas aeruginosa. Methods: The …
Rationale: Acute lung injury (ALI) is a serious condition in critically ill patients that predisposes to secondary bacterial pneumonia. Vascular leak is a hallmark in the pathogenesis of ALI. The fibrin-derived peptide Bβ15–42 was shown to preserve endothelial barriers, thereby reducing vascular leak. The potential therapeutic role of Bβ15–42 in ALI has not been addressed so far.
Objectives: To investigate the therapeutic potential of Bβ15–42 in ALI and secondary pneumonia induced by Pseudomonas aeruginosa.
Methods: The effect of the fibrin-derived peptide Bβ15–42 was studied in models of ALI, induced either by pulmonary administration of LPS or hydrochloric acid. Lung inflammation was analyzed by quantifying cell influx, cytokine levels, and oxidized lipids. Vascular leak was determined by Evans Blue extravasations and alveolar protein content. In subsequent two-hit studies, mice were infected with P. aeruginosa 24 hours after induction of aspiration pneumonitis and effects of Bβ15–42 on inflammation, bacterial clearance, and survival were evaluated.
Measurements and Main Results: After LPS or acid inhalation, proinflammatory cytokine levels, neutrophil influx, and vascular leak were found diminished in mice treated with Bβ15–42. Acid aspiration impaired macrophage functions and rendered mice more susceptible to subsequent P. aeruginosa infection, whereas mice that received Bβ15–42 during acid aspiration and were subsequently challenged with bacteria displayed reduced inflammation, enhanced bacterial clearance, and ultimately improved survival.
Conclusions: The fibrin-derived peptide Bβ15–42 exerted protective effects during ALI, resulting in diminished lung injury and preserved antibacterial properties of macrophages, which improved outcome during subsequent P. aeruginosa pneumonia.
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