Comparison of the effect of LPS and PAM3 on ventilated lungs

• Published in: BMC pulmonary medicine 2010-04, Vol.10 (1), p.20-20, Article 20
• Main Authors: Hauber, Hans P, Karp, Dörte, Goldmann, Torsten, Vollmer, Ekkehard, Zabel, Peter
• Format: Article
• Language: English
• Subjects: Airway Resistance - drug effects; Airway Resistance - physiology; Animals; Artificial respiration; Bacteria, Pathogenic; Chemokine CXCL2 - metabolism; Complications and side effects; Dose-Response Relationship, Drug; Gram-Negative Bacteria - metabolism; Gram-Positive Bacteria - metabolism; Health aspects; Inflammation; Lipopeptides - metabolism; Lipopeptides - pharmacology; Lipopolysaccharides; Lipopolysaccharides - metabolism; Lipopolysaccharides - pharmacology; Lung - cytology; Lung - drug effects; Lung - physiology; Lung Compliance - drug effects; Lung Compliance - physiology; Male; Mice; Mice, Inbred C57BL; Models, Animal; Neutrophils - cytology; Neutrophils - drug effects; Physiological aspects; Research article; Respiration, Artificial; Risk factors; Tumor Necrosis Factor-alpha - metabolism; Ventilator-associated pneumonia
• ISSN: 1471-2466; 1471-2466
• DOI: 10.1186/1471-2466-10-20

While lipopolysaccharide (LPS) from Gram-negative bacteria has been shown to augment inflammation in ventilated lungs information on the effect of Gram-positive bacteria is lacking. Therefore the effect of LPS and a lipopetide from Gram-positive bacteria, PAM3, on ventilated lungs were investigated. C57/Bl6 mice were mechanically ventilated. Sterile saline (sham) and different concentrations of LPS (1 microg and 5 microg) and PAM3 (50 nM and 200 nM) were applied intratracheally. Lung function parameters and expression of MIP-2 and TNFalpha as well as influx of neutrophils were measured. Mechanical ventilation increased resistance and decreased compliance over time. PAM3 but not LPS significantly increased resistance compared to sham challenge (P < 0.05). Both LPS and PAM3 significantly increased MIP-2 and TNFalpha mRNA expression compared to sham challenge (P < 0.05). The numbers of neutrophils were significantly increased after LPS at a concentration of 5 microg compared to sham (P < 0.05). PAM3 significantly increased the numbers of neutrophils at both concentrations compared to sham (P < 0.05). These data suggest that PAM3 similar to LPS enhances ventilator-induced inflammation. Moreover, PAM3 but not LPS increases pulmonary resistance in ventilated lungs. Further studies are warranted to define the role of lipopetides in ventilator-associated lung injury.