Characterization of a Murine Model of Endotoxin-Induced Acute Lung Injury

Kabir, K.; Gelinas, Jean Pierre; Chen, Meihong; Chen, Dongfen; Zhang, Dexin; Luo, Xiaoxing; Yang, Jiani; Carter, Darryl; Rabinovici, Reuven

doi:10.1097/00024382-200204000-00010

Cited by 140 publications

(102 citation statements)

References 23 publications

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“…24 h, and was resolving by 48 h. Pulmonary edema as determined by lung wet-to-dry weight ratios was apparent by 2 h, peaked at 6 h, and then gradually declined, but lung water remained elevated even at 48 h. The early and transient alterations in lung function are consistent with the time course of inflammatory cytokine release and pulmonary edema in our studies and as reported in studies of lethal murine endotoxemia (12,18). The fact that the time of maximum edema came 6 h after endotoxin is also identical to the time course of edema in the reported studies of lethal endotoxemia (18).…”

Section: Discussionsupporting

confidence: 90%

Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses

Rojas

Woods

Mora

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

208

149

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-Acute lung injury is usually a complication of sepsis, and endotoxin treatment of mice is a frequently used experimental model. To define this model and to clarify pathogenesis of the lung injury, we injected with 1 mg/kg endotoxin ip and measured pulmonary function, pulmonary edema, serum concentrations of cytokines and growth factors, and lung histology over 48 h. During the first 6 h, tidal volume and minute volume increased and respiratory frequency decreased. Serum concentrations of cytokines showed three patterns: 10 cytokines peaked at 2 h and declined rapidly, two peaked at 6 h and declined, and two had biphasic peaks at 2 and 24 h. Growth factors increased later and remained elevated longer. Both collagen and fibronectin were deposited in the lungs beginning within hours of endotoxin and resolving over 48 h. Histologically, lungs showed increased cellularity at 6 h with minimal persistent inflammation at 48 h. Lung water peaked at 6 h and gradually decreased over 48 h. We conclude that intraperitoneal administration of endotoxin to mice causes a transient systemic inflammatory response and transient lung injury and dysfunction. The response is characterized by successive waves of cytokine release into the circulation, early evidence of lung fibrogenesis, and prolonged increases in growth factors that may participate in lung repair. acute lung injury; acute respiratory distress syndrome; cytokines; growth factors; lipopolysaccharide; animal model ACUTE LUNG INJURY (ALI) is a clinical syndrome associated with respiratory dysfunction often as a complication of sepsis and with ϳ50% mortality (16). The pathophysiology of ALI involves inflammation (11) with diffuse alveolar damage, increased capillary permeability, interstitial and alveolar edema, influx of circulating inflammatory cells, and formation of hyaline membranes.Because the most common cause of ALI in humans is sepsis, administration of gram-negative bacterial endotoxin lipopolysaccharide (LPS) has been used as an animal model of sepsisrelated lung injury in several species (5,7,13,14,25). Endotoxin is a biologically active component of the gramnegative bacterial cell wall that exists as complexes of LPS and protein. Low-dose exposure to LPS activates macrophages (21) and polymorphonuclear cells, presumably aimed at eliminating the toxic agent, whereas higher doses cause tissue injury. Although virtually all mammalian species react to endotoxin, species sensitivity is highly variable (22).Although LPS is often used as a stimulus for lung injury in mice, the pathophysiology of this model has not been thoroughly described. To maximize pathogenetic information from this model and permit comparisons to data from human studies, it is important to delineate the time course of the biochemical, functional, and structural alterations induced by endotoxin. To accomplish those goals, we conducted studies in C57BL/6 mice. We measured body weight, pulmonary function (plethysmograph), total lung water (wet-dry lung weight), serum concentrations of cytokines and...

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Section: Discussionsupporting

confidence: 90%

Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses

Rojas

Woods

Mora

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

208

149

View full text Add to dashboard Cite

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“…3B). This observation is in agreement with a previous report in mice given intraperitoneal endotoxin (31). In addition, lung IL-4 (a Th2 cytokine) levels were significantly enhanced at 24 and 48 h in the LPS-induced ALI mice (Fig.…”

Section: Losartan Inhibits Th1 and Th17 Polarization Responses In Lpssupporting

confidence: 93%

Losartan inhibits conventional dendritic cell maturation and Th1 and Th17 polarization responses: Νovel mechanisms of preventive effects on lipopolysaccharide-induced acute lung injury

Zhang²,

Yu³

et al. 2011

Int J Mol Med

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Abstract. Acute lung injury (ALI) remains one of major causes of morbidity and mortality in intensive care medicine. The lack of efficient pharmacological interventions contributes to the high mortality rate of ALI. Losartan, an antagonist of angiotensin II (Ang II) type 1 receptor, is a potent therapeutic drug for ALI. Recent reports suggest that losartan inhibits the maturation of dendritic cells (DCs), impairs T-helper (Th) 1 immune response and ultimately attenuates inflammation in several Ang II-mediated inflammatory diseases. However, the possible protective mechanisms of losartan in ALI remain poorly understood. This study was aimed to define the effect of losartan on the frequency and phenotype of respiratory conventional DCs (cDCs) and Th cells polarization in lipopolysaccharide (LPS)-induced ALI mice. Results demonstrate that early after induction of LPS-induced ALI, cDCs expressing modest amounts of CD80 rapidly accumulated in the lungs. In addition, polarized Th1 and Th17 responses were markedly increased in LPS-induced ALI mice at 24 and 48 h. Of note, losartan led to inhibition of respiratory cDCs maturation at 6 h and suppressed Th1 and Th17 polarization responses compared with ALI mice at 24 and 48 h. Collectively, our findings may provide a novel and, at least, partial explanation for the protective effects by which losartan inhibits lung cDCs maturation and suppresses Th1 and Th17 immune responses.

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“…The LPS-induced ALI animal model is a common experimental model used for the investigation of molecular mechanisms and drug efficacy in ALI (28). To observe the effect of eriodictyol on ALI, an LPS-induced ALI animal model was therefore established.…”

Section: Resultsmentioning

confidence: 99%

Eriodictyol, a plant flavonoid, attenuates LPS-induced acute lung injury through its antioxidative and anti-inflammatory activity

Zhu

Guo

Huang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Acute lung injury (ALI) is characterized by excessive inflammatory responses and oxidative injury in the lung tissue. It has been suggested that anti-inflammatory or antioxidative agents could have therapeutic effects in ALI, and eriodictyol has been reported to exhibit antioxidative and anti-inflammatory activity in vitro. The aim of the present study was to investigate the effect of eriodictyol on lipopolysaccharide (LPS)-induced ALI in a mouse model. The mice were divided into four groups: Phosphate-buffered saline-treated healthy control, LPS-induced ALI, vehicle-treated ALI (LPS + vehicle) and eriodictyol-treated ALI (LPS + eriodictyol). Eriodictyol (30 mg/kg) was administered orally once, 2 days before the induction of ALI. The data showed that eriodictyol pretreatment attenuated LPS-induced ALI through its antioxidative and anti-inflammatory activity. Furthermore, the eriodictyol pretreatment activated the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway in the ALI mouse model, which attenuated the oxidative injury and inhibited the inflammatory cytokine expression in macrophages. In combination, the results of the present study demonstrated that eriodictyol could alleviate the LPS-induced lung injury in mice by regulating the Nrf2 pathway and inhibiting the expression of inflammatory cytokines in macrophages, suggesting that eriodictyol could be used as a potential drug for the treatment of LPS-induced lung injury.

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Characterization of a Murine Model of Endotoxin-Induced Acute Lung Injury

Cited by 140 publications

References 23 publications

Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses

Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses

Losartan inhibits conventional dendritic cell maturation and Th1 and Th17 polarization responses: Νovel mechanisms of preventive effects on lipopolysaccharide-induced acute lung injury

Eriodictyol, a plant flavonoid, attenuates LPS-induced acute lung injury through its antioxidative and anti-inflammatory activity

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