Animal models of acute lung injury

ArticleinAJP Lung Cellular and Molecular Physiology 295(3):L379-99 · August 2008with34 Reads
DOI: 10.1152/ajplung.00010.2008 · Source: PubMed
Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.
    • "Sepsis due to non pulmonary infections, aspiration of gastric contents, major surgery or trauma can also induce the injury [2,4] . LPS inhalation mimics human Gram-negative ALI, inducing neutrophil recruitment, pulmonary edema and finally impairment of gas exchange [5]. Recruitment of neutrophils is a key event in development of ALI [4] leading to plasma leakage and deterioration of oxygenation. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Recruitment of neutrophils into the lungs, regarded as a key mechanism in progression of ALI, depends on signaling between neutrophils and platelets. Consequently we explored the effect of platelet-targeted aspirin and tirofiban treatment in endotoxin induced acute lung injury. Methods: C57Bl/6 mice were exposed to aerosolized LPS (500μg/ml) for 30min and treated with Aspirin (100μg/g bodyweight via intraperitoneal injection, 30 min before or 1 hour after LPS inhalation) or Tirofiban (0.5μg/ g bodyweight via tail vein injection 30 min before or 1 hour after LPS inhalation). The count of alveolar, interstitial, and intravascular neutrophils was assessed 4h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and protein content in the BAL fluid. Results: Aspirin both before and after LPS inhalation reduced neutrophil influx into the lung and lung permeability indicating the protective role of Aspirin in ALI. Tirofiban, however, did not alter neutrophil recruitment after LPS inhalation. Release of platelet-derived chemokines CCL5 and PF4 and neutrophil extracellular traps was reduced by Aspirin but not by Tirofiban. Conclusion: Aspirin, but not Tirofiban reduces neutrophil recruitment and displays protective effects during endotoxin induced lung injury.
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    • "In this regard , future studies examining the consequences of acute and chronic hypercholesterolemia across multiple species of both sexes, with a more detailed focus on the intracellular cholesterol metabolism, are warranted. In order to thoroughly investigate the effects of a high cholesterol diet we utilized three distinct experimental models of lung injury [30]. Acid aspiration, reflecting gastric aspiration as it occurs in patients, provided a clinically relevant model to assess the effect of heightened serum cholesterol on lung injury. "
    [Show abstract] [Hide abstract] ABSTRACT: Acute respiratory distress syndrome (ARDS) is a pulmonary disorder associated with alterations to the pulmonary surfactant system. Recent studies showed that supra-physiological levels of cholesterol in surfactant contribute to impaired function. Since cholesterol is incorporated into surfactant within the alveolar type II cells which derives its cholesterol from serum, it was hypothesized that serum hypercholesterolemia would predispose the host to the development of lung injury due to alterations of cholesterol content in the surfactant system.
    Full-text · Article · Jun 2016
    • "All these data suggested that LFG-500 could prevent the accumulation of neutrophils and macrophages in the lung tissues. As the primary features of inflammation in ALI animals, elevations of relevant inflammatory mediators, including cytokines, chemokines, and adhesion molecules, drive more neutrophils and aggravate the damage to lung tissues [45,46] . Especially, LPS signals through the Toll-like receptor 4, leading to a rapid release of proinflammatory cytokines, such as TNF-a, which activates multiple downstream effectors to induce the production of IL-1b and IL- 6, thereby amplifying the inflammatory response and promoting LPS-induced ALI [47]. "
    [Show abstract] [Hide abstract] ABSTRACT: Acute lung injury (ALI) often causes significant morbidity and mortality worldwide. Improved treatment and effective strategies are still required for ALI patients. Our previous studies demonstrated that LFG-500, a novel synthesized flavonoid, has potent anti-cancer activities, while its anti-inflammatory effect has not been revealed. In the present study, the in vivo protective effect of LFG-500 on the amelioration of lipopolysaccharide (LPS)-induced ALI and inflammation was detected. LFG-500 attenuated LPS-induced histological alterations, suppressed the infiltration of inflammatory cells in lung tissues and bronchoalveolar lavage fluid, as well as inhibited the secretion of several inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in lung tissues after LPS challenge. In addition, the in vitro effects and mechanisms were studied in LPS stimulated RAW 264.7 cells and THP-1 cells. LFG-500 significantly decreased the secretion and expression of TNF-α, IL-1β, and IL-6 through inhibiting the transcriptional activation of NF-κB. Moreover, overexpression of NF-κB p65 reversed the inhibitory effect of LFG-500 on LPS-induced NF-κB activation and inflammatory cytokine secretion. Further elucidation of the mechanism revealed that p38 and JNK MAPK pathways were involved in the anti-inflammation effect of LFG-500, through which LFG-500 inhibited the classical IKK-dependent pathway and led to inactivation of NF-κB. More importantly, LFG-500 suppressed the expression and nuclear localization of NF-κB in LPS-induced ALI mice. Taken together, these results demonstrated that LFG-500 could attenuate LPS-induced ALI and inflammation by suppressing NF-κB activation, which provides new evidence for the anti-inflammation activity of LFG-500.
    Full-text · Article · May 2016
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