Priming with endotoxin increases acute lung injury in mice by enhancing the severity of lung endothelial injury.

Journal Article (Journal Article)

Endotoxin-induced acute lung injury (ALI) is a commonly used model. However, the effect of a priming dose of endotoxin on lung fluid balance has not been well studied. We hypothesized that endotoxin-induced ALI in mice would be enhanced under a priming condition. Mice were intratracheally (IT) instilled with either a priming dose of endotoxin from E. coli (0.5 mg/kg) or equal volume of PBS. Eighteen hours later, a larger challenge dose of endotoxin (5 mg/kg) was given IT. Control mice received PBS only. After 24 hr, the mice were sacrificed and the degree of lung injury and inflammation were measured. Endotoxin priming increased body weight loss and worsened hypothermia. Extravascular lung water and lung endothelial permeability were higher in the primed group. Priming with endotoxin reduced alveolar fluid clearance; however, there was no effect on bronchoalveolar lavage (BAL) levels of receptor for advanced glycation end products (RAGE). The primed group had increased alveolar inflammation as demonstrated by increased numbers of neutrophils in the BAL. There was no significant difference in NF-κB p65 in the lung nuclear extract among the experimental groups. Taken together, priming with a small dose of endotoxin followed by a larger challenge dose of endotoxin induces more systemic illness and increased pulmonary edema in mice, largely due to increased lung endothelial permeability and lung inflammation. This model should be useful to investigators studying ALI who want to simulate the clinical setting in which more than one insult often leads to greater clinical lung injury.

Full Text

Duke Authors

Cited Authors

  • Lee, JS; Su, X; Rackley, C; Matthay, MA; Gupta, N

Published Date

  • January 2011

Published In

Volume / Issue

  • 294 / 1

Start / End Page

  • 165 - 172

PubMed ID

  • 21157927

Pubmed Central ID

  • PMC3072226

Electronic International Standard Serial Number (EISSN)

  • 1932-8494

Digital Object Identifier (DOI)

  • 10.1002/ar.21244


  • eng

Conference Location

  • United States