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Characterization of a murine model of endotoxin-induced acute lung injury
Koroush Kabir1, Jean-Pierre Gelinas, Meihong Chen
1Section of Trauma and Surgical Critical Care, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Abstract:
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.
Insights
Endotoxin administration in mice effectively models acute respiratory distress syndrome (ARDS) by inducing microvascular lung injury, characterized by inflammation, edema, and mortality. This study comprehensively characterizes this mouse model for ARDS research.
Area of Science:
- * Pulmonary Medicine
- * Immunology
- * Toxicology
Background:
- * Acute Respiratory Distress Syndrome (ARDS) is a critical condition often studied using animal models.
- * Endotoxin-induced microvascular lung injury in mice is a widely adopted model for ARDS research.
- * Comprehensive characterization of this model is essential for reliable experimental outcomes.
Purpose of the Study:
- * To systematically characterize the murine model of endotoxin-induced microvascular lung injury.
- * To evaluate the temporal progression of inflammatory responses and tissue damage following endotoxin administration.
- * To establish the utility of this model for studying ARDS.
Main Methods:
- * Male C57bl/6 mice were administered an LD55 dose of E. coli endotoxin (15 mg/kg, i.p.).
- * Lungs were harvested at various time points post-administration.
- * Analysis included inflammatory mediator expression, leukocyte accumulation (myeloperoxidase activity), pulmonary edema (lung water content), and histopathology.
Main Results:
- * Early (1-2 h) induction of multiple inflammatory mediators (e.g., IL-1α, IL-1β, IL-4, IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP-1).
- * Significant leukocyte accumulation in lung tissue (P < 0.05) and development of pulmonary edema (P < 0.05).
- * Histopathological findings consistent with acute microvascular lung injury and increased mortality.
Conclusions:
- * The endotoxin-induced murine model recapitulates key features of human ARDS.
- * This study provides a detailed characterization of the model's inflammatory and injury parameters.
- * The findings support the use of this model for advancing ARDS research.