Comparison of the effect of LPS and PAM3 on ventilated lungs.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Hauber
Hans P
HP
Pathophysiology of Inflammation, Research Center Borstel, Borstel, Germany. hphauber@fz-borstel.de
Karp
Dörte
D
Goldmann
Torsten
T
Vollmer
Ekkehard
E
Zabel
Peter
P
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D054426:Chemokine CXCL2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D006094:Gram-Positive Bacteria / Q000378:metabolism*; D055666:Lipopeptides / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D012121:Respiration, Artificial; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D055666:Lipopeptides; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha
Eur Respir J. 2001 May;17(5):1034-45
11488306
Anesth Analg. 2001 Feb;92(2):428-36
11159246
J Appl Physiol (1985). 1989 Mar;66(3):1059-64
2708231
Anesthesiology. 2008 Sep;109(3):465-72
18719444
J Clin Invest. 1997 Mar 1;99(5):944-52
9062352
Crit Care Med. 1993 Jan;21(1):131-43
8420720
Crit Care Med. 1990 Jun;18(6):634-7
2344755
Am Rev Respir Dis. 1988 May;137(5):1159-64
3057957
JAMA. 1999 Jul 7;282(1):54-61
10404912
Am J Respir Crit Care Med. 2002 Apr 1;165(7):867-903
11934711
Am J Respir Crit Care Med. 1994 May;149(5):1327-34
8173774
Monaldi Arch Chest Dis. 1993;48(2):134-9
8518775
Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1547-52
11029375
J Immunol. 2005 Sep 1;175(5):3369-76
16116230
J Appl Physiol (1985). 1990 Sep;69(3):956-61
2123181
Am Rev Respir Dis. 1990 Aug;142(2):311-5
2200314
J Endotoxin Res. 2002;8(6):459-63
12697090
Am J Physiol Lung Cell Mol Physiol. 2004 Sep;287(3):L533-42
15145786
Crit Care. 2003 Jun;7(3):233-41
12793874
Am J Respir Crit Care Med. 2006 Mar 15;173(6):653-8
16387799