Characterization of a murine model of endotoxin-induced acute lung injury.
Endotoxin-induced microvascular lung injury in mice is a commonly used experimental model of the acute respiratory distress syndrome (ARDS). The present paper aimed to characterize this popular model in a comprehensive and systematic fashion. Male C57bl/6 mice (n = 5) were administered an LD55 dose of E. coli endotoxin (15 mg/kg, i.p.), and lungs were harvested at several time points and evaluated for injury as well as for expression of a variety of inflammatory mediators. Endotoxin induced many features characteristic of acute microvascular lung injury. These included early (1-2 h) expression of inflammatory mediators (IL-1alpha, IL-1beta, IL-4, IL-6, IL-10, TNF-alpha, interferon-alpha, interferon gamma, and MCP-1) and leukocyte accumulation in lung tissue (lung myeloperoxidase activity 18.5 +/- 7.8 U/g tissue, P < 0.05), followed by pulmonary edema (lung water content index 17.4% +/- 2.5%, P < 0.05) and mortality. Histopathological evaluation of lung tissue was compatible with these findings. The characterization of this murine model of endotoxin-induced microvascular injury will facilitate its utilization in ARDS research.
Kabir
Koroush
K
Section of Trauma and Surgical Critical Care, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Gelinas
Jean-Pierre
JP
Chen
Meihong
M
Chen
Dongfen
D
Zhang
Dexin
D
Luo
Xiaoxing
X
Yang
Jing-Hua
JH
Carter
Darryl
D
Rabinovici
Reuven
R
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000209:etiology
D018925:Chemokines; D016207:Cytokines; D004731:Endotoxins; D018836:Inflammation Mediators; D012333:RNA, Messenger; D009195:Peroxidase