Evolution of Endotoxin-Induced Lung Injury in the Rat beyond the Acute Phase

Domenici, L.; Pieri, Laura; Gallè, M.B.; Romagnoli, Paolo; Adembri, Chiara

doi:10.1159/000074418

Cited by 12 publications

(9 citation statements)

References 28 publications

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“…As previously described, LPS induced a patchy inflammation [1], with regions of no or mild inflammation amidst areas of extensive inflammation. In the regions of mild and moderate inflammation, apoptosis and subsequent macrophage phagocytosis carried out swift and silent neutrophil elimination, resulting in sufficient clearance of infiltrating neutrophils.…”

Section: Discussionsupporting

confidence: 63%

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Direct evidence of secondary necrosis of neutrophils during intense lung inflammation

Rydell‐Törmänen¹

2006

European Respiratory Journal

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Several pulmonary inflammatory conditions are characterised by infiltration of neutrophils. Normally, neutrophils are silently removed by apoptosis, followed by phagocytosis. However, if phagocytosis fails, apoptotic cells undergo secondary necrosis. Recent findings of increased levels of the pan-necrosis marker lactate dehydrogenase in bronchoalveolar lavage from lipopolysaccharide-exposed mice implies potential involvement of secondary necrosis. Using a similar model, this study aimed to identify the source of lactate dehydrogenase and to search for direct histological evidence of secondary necrosis.Lipopolysaccharide (LPS) was administered to the lungs of BALB/c mice, and bronchoalveolar lavage and tissue samples were collected 4, 12, 24, 36, 48, 60 and 72 h after administration. LPS induced a patchy neutrophil-rich lung inflammation, where the numbers of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling-positive neutrophils were increased at 12 h and onwards. Lavage levels of neutrophils and lactate dehydrogenase increased significantly at 4 and 24 h, respectively. Detailed electron microscopic assessment of neutrophil activation and death modes revealed that up to 14% of the neutrophils were undergoing secondary necrosis, whereas apoptotic or primary necrotic structural cells were rarely found.In summary, this study provides direct evidence that secondary necrosis of neutrophils is a common process during intense lung inflammation. This implies that neutrophil apoptosis may cause rather than resolve airway inflammation.

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Section: Discussionsupporting

confidence: 63%

“…Experimental pulmonary exposure of lipopolysaccharide (LPS) induces a fast and intense neutrophil response [1]. Under normal physiological conditions, neutrophils are silently and swiftly eliminated through apoptosis, followed by phagocytosis by alveolar macrophages [2].…”

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confidence: 99%

Direct evidence of secondary necrosis of neutrophils during intense lung inflammation

Rydell‐Törmänen¹

2006

European Respiratory Journal

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“…However, other researchers consider that the one-hit model is more effective than the two-hit model, due to the reproducibility, rapid onset of clinical symptoms and lack of expense. Similarly, a previous study suggested that the introduction of a second hit has no impact on inflammation or increased lung injury (6). Therefore, based on previous findings, the present study aimed to investigate and compare the two models using [ 18 F]fluorodeoxyglucose (FDG) micro-positron emission tomography (microPET) to evaluate the inflammatory response in the lungs in these models.…”

Section: Introductionmentioning

confidence: 69%

Evaluation of the inflammatory response in a two-hit acute lung injury model using [18F]FDG microPET

Zhou

Jiang

Zhang

et al. 2013

Experimental and Therapeutic Medicine

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The aim of this study was to investigate whether a two-hit acute lung injury (ALI) model is better than a one-hit model in simulating ALI, and to evaluate the inflammatory response in the lungs in these two models using micro-positron emission tomography (microPET) with [18F]fluorodeoxyglucose (FDG). Sprague Dawley rats were divided into four groups; rats in the lipopolysaccharide (LPS; n=10) and LPS-HCl (n=10) groups were challenged by the intraperitoneal administration of 5 mg/kg LPS, while rats in the normal saline (NS; n=3) and HCl (n=10) groups received the same volume of normal saline solution. Sixteen hours following the administration, the rats in the HCl and LPS-HCl groups received an acid instillation (IT) of 0.5 ml/kg HCl (pH=1.2), while the rats in the remaining two groups received the same volume of normal saline solution. The mean arterial blood pressure (MAP) and blood gas concentrations were measured in all four groups. MicroPET was performed 4 h following HCl IT and the lungs were excised for histopathological examination. The rats in the LPS-HCl group exhibited a higher arterial PaO2 and a lower arterial PaCO2 compared with the rats in the remaining groups. The MAP decreased markedly in the LPS-HCl group, but remained stable in the LPS, HCl and NS groups. MicroPET results identified that the region of interest ratio in the LPS-HCl group (9.00±1.41) was significantly higher compared with those in the LPS (4.01±0.60) and HCl (3.33±0.55) groups (P<0.01). In addition, histological examination showed that the mean lung injury score in the LPS-HCl group (12.70±0.95) was significantly higher compared with those in the HCl (8.40±1.26) and LPS (7.00±0.82) groups (P<0.01). The present study demonstrates that LPS pretreatment significantly magnifies and prolongs the inflammatory response to subsequent acid IT in the lungs. Moreover, it is simpler to induce ALI using the two-hit model than with the one-hit model, and [18F]FDG microPET is a useful tool for evaluating the inflammatory reaction during ALI.

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“…9 In rats, acute exposure to intratracheal LPS alters lung histology even after 16 days beyond the acute exposure, with a resulting increase in extracellular matrix, differentiation of myofibroblasts, and altered secretion of surfactant by newly differentiated type II pneumocytes. 10 Textile workers who developed byssinosis (thought now to be caused mainly by chronic occupational endotoxin exposure) developed severe obstructive airway disease. 11 Similarly, swine confinement workers developed symptomatic chronic airflow obstruction; corresponding histology revealed thickening of the airway basement that was similar to COPD.…”

Section: Abbreviations Usedmentioning

confidence: 99%