Lipopolysaccharide (LPS) Induced Lung-Injury

Bacterial pneumonia may trigger the development of acute lung injury (ALI) and/or acute respiratory distress (ARDS). Some of the key pathological features of ALI/ARDS include an acute inflammatory response in the alveoli and endothelial injury. Complications of these conditions are pulmonary hypo/hypertension and myocardial depression. The murine acute lung injury model is able to mimic the cascade of inflammatory responses common to ALI/ARDS in humans and is a platform for testing the efficacy of novel compounds that may aid in protecting against the development of this condition.

Category(s)

Preclinical Drug Efficacy Studies

Species

Mice

Basic Methodology

Animals are anesthetized, orally intubated with a sterile plastic catheter and challenged with an intratracheal instillation of LPS. At study completion lungs are lavaged with 3 ml of saline. Lavage fluid is collected for downstream measures. The administration of compounds is performed according to the schedule set-forth in the study protocol.

Measurements

Clinical observations, body weight, collection of BAL for total cell counts, cytokine/chemokine profiling using ELISA and Luminex multiplex assays, and flow cytometric analysis of macrophages

Reference Substance(s):

Dexamethasone

Literature References:

Kitamura Y, Hashimoto S, Mizuta N, Kobayashi A, Kooguchi K, Fujiwara I, Nakajima H. (2001) Fas/FasL-dependent Apoptosis of Alveolar Cells after Lipopolysaccharide-induced Lung Injury in Mice. American Journal of Respiratory and Critical Care Medicine; 163: 762-9.

Kristof AS, Goldberg P, Laubach V, Hussain SNA. (1998) Role of Inducible Nitric Oxide Synthase in Endotoxin-Induced Acute Lung Injury. American Journal of Respiratory and Critical Care Medicine; 158: 1883-89.

Martin TR, Mathison JC, Tobias PS, Leturcq DJ, Moriarty AM, Maunder RJ, Ulevitch RJ. (1992) Effects of Lipopolysaccharide Binding Protein on Alveolar Macrophages. The Journal of Clinical Investigation; 90: 2209-19.