Acid and particulate-induced aspiration lung injury in mice: importance of MCP-1

Raghavendran, Krishnan; Davidson, Bruce A.; Mullan, Barbara A.; Hutson, Alan D.; Russo, Thomas A.; Manderscheid, Patricia A.; Woytash, James A.; Holm, Bruce A.; Notter, Robert H.; Knight, Paul R.

doi:10.1152/ajplung.00390.2004

Cited by 60 publications

(79 citation statements)

References 34 publications

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“…The levels of IL-1b were increased in the mice subjected to LC when compared with corresponding control animals, as has been previously reported (11). There was no significant difference in the levels of IL-1b between the two injury groups at 5 hours after LC, but there was a significant increase in its levels at the 24-, 48-, and 72-hour time points after LC in the CCR2 2/2 genotype when compared with WT ( Figure 6A).…”

Section: Inflammation After Lcsupporting

confidence: 86%

“…Individual intergroup comparisons were analyzed using the two-tailed unpaired t test with Welch's correction. A value of P less than 0.05 was considered significant (10,11).…”

Section: Discussionmentioning

confidence: 99%

“…We have shown that elevated levels of CCL-2 in the bronchoalveolar lavage (BAL) are associated with improved oxygenation in LC injury in rats (10). We have also reported increased mortality, persistent inflammation, and decreased granulomatous compartmentalization in CCL-2 knockout mice injured with gastric aspiration (11). Amano and colleagues (12) showed, using a Pseudomonas aeruginosa pneumonia model of lung injury, that administration of CCL-2-neutralizing antibody increased neutrophil infiltration and lung injury and reduced phagocytic activity of alveolar macrophages (AMs) for apoptotic neutrophils (12).…”

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confidence: 97%

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Role of Macrophage Chemoattractant Protein-1 in Acute Inflammation after Lung Contusion

Suresh

Machado-Aranda

et al. 2012

Am J Respir Cell Mol Biol

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Lung contusion (LC), commonly observed in patients with thoracic trauma is a leading risk factor for development of acute lung injury/ acute respiratory distress syndrome. Previously, we have shown that CC chemokine ligand (CCL)-2, a monotactic chemokine abundant in the lungs, is significantly elevated in LC. This study investigated the nature of protection afforded by CCL-2 in acute lung injury/acute respiratory distress syndrome during LC, using rats and CC chemokine receptor (CCR) 2 knockout (CCR2 2/2 ) mice. Rats injected with a polyclonal antibody to CCL-2 showed higher levels of albumin and IL-6 in the bronchoalveolar lavage and myeloperoxidase in the lung tissue after LC. Closed-chest bilateral LC demonstrated CCL-2 localization in alveolar macrophages (AMs) and epithelial cells. Subsequent experiments performed using a murine model of LC showed that the extent of injury, assessed by pulmonary compliance and albumin levels in the bronchoalveolar lavage, was higher in the CCR2 2/2 mice when compared with the wild-type (WT) mice. We also found increased release of IL-1b, IL-6, macrophage inflammatory protein-1, and keratinocyte chemoattractant, lower recruitment of AMs, and higher neutrophil infiltration and phagocytic activity in CCR2 2/2 mice at 24 hours. However, impaired phagocytic activity was observed at 48 hours compared with the WT. Production of CCL-2 and macrophage chemoattractant protein-5 was increased in the absence of CCR2, thus suggesting a negative feedback mechanism of regulation. Isolated AMs in the CCR2 2/2 mice showed a predominant M1 phenotype compared with the predominant M2 phenotype in WT mice. Taken together, the above results show that CCL-2 is functionally important in the down-modulation of injury and inflammation in LC.Keywords: lung contusion; macrophage chemoattractant protein-1; CC chemokine ligand-2; CC chemokine receptor 2; inflammation Thoracic injury is involved in nearly one-third of all acute trauma admissions (1-4), often including clinically significant lung contusion (LC) with subsequent respiratory deficits. LC is an important independent risk factor for the development of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and ventilator-associated pneumonia in affected patients (1-4), all of which are associated with high mortality and morbidity (5).The clinical pathophysiology of LC includes hypoxemia, hypercarbia, increased work of breathing, and decreased lung volumes and compliance in association with ventilation-perfusion mismatching, intrapulmonary shunting, edema, and segmental lung damage (1, 6, 7). As 30% of patients with LC progress to ALI/ ARDS (1), it is important to delineate the factors responsible for the development of progressive respiratory failure. Several lines of evidence suggest that factors in addition to traumainduced tissue damage may contribute to respiratory failure in LC (1, 3).Macrophage chemoattractant protein (MCP)-1/CC chemokine ligand (CCL)-2 is produced by a number of cells in response to inflammatory stimuli, suc...

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Section: Inflammation After Lcsupporting

confidence: 86%

“…Individual intergroup comparisons were analyzed using the two-tailed unpaired t test with Welch's correction. A value of P less than 0.05 was considered significant (10,11).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

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Role of Macrophage Chemoattractant Protein-1 in Acute Inflammation after Lung Contusion

Suresh

Machado-Aranda

et al. 2012

Am J Respir Cell Mol Biol

Self Cite

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“…This modification should be widely accessible to most laboratories (104) wanting to study fibroproliferation as a result of ALI/ARDS. Similar models in both rats and mice have used a combination of acid and particulate matter to mimic clinically relevant aspiration events in human subjects (101,105). A combination insult of acid with particulate matter induces synergistic and progressive lung injury, and therefore is likely to result in severe interstitial pulmonary fibrosis (101).…”

Section: Acid Instillation-associated Fibroproliferative Lung Injurymentioning

confidence: 99%

“…During the past decade, multiple small-animal models of lung contusion-induced fibrotic injury have been established to fill this gap (102,105,112,113). Using rats, a bilateral lung contusion without associated cardiac injury is induced in anesthetized animals by dropping a 0.3-kg hollow cylindrical weight onto a mobile plate with a precordial shield (102).…”

Section: Lung Contusion-induced Fibrosismentioning

confidence: 99%

Animal Models of Fibrotic Lung Disease

Moore

Lawson

Oury

et al. 2013

Am J Respir Cell Mol Biol

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350

308

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Interstitial lung fibrosis can develop as a consequence of occupational or medical exposure, as a result of genetic defects, and after trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can develop in an idiopathic manner. The pathogenesis of each form of lung fibrosis remains poorly understood. They each result in a progressive loss of lung function with increasing dyspnea, and most forms ultimately result in mortality. To better understand the pathogenesis of lung fibrotic disorders, multiple animal models have been developed. This review summarizes the common and emerging models of lung fibrosis to highlight their usefulness in understanding the cell-cell and soluble mediator interactions that drive fibrotic responses. Recent advances have allowed for the development of models to study targeted injuries of Type II alveolar epithelial cells, fibroblastic autonomous effects, and targeted genetic defects. Repetitive dosing in some models has more closely mimicked the pathology of human fibrotic lung disease. We also have a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis. Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease.Keywords: fibrosis; collagen; fibroblast; aging; cytokines Interstitial lung disease is often associated with the development of chronic fibrosis. These diseases are characterized clinically by progressive dyspnea, cough, restrictive physiology, and impaired gas exchange. Humans manifest many types of fibrotic lung disease (1). Among the diffuse parenchymal lung disorders (DPLDs) are diseases of known cause (e.g., drug-related, environmental exposures, or those associated with collagen vascular disease), the idiopathic interstitial pneumonias (IIPs), the granulomatous DPLDs (e.g., sarcoidosis), and rare noncategorized diseases, such as lymphangioleiomyomatosis. Idiopathic pulmonary fibrosis (IPF) is the most common disease within the category of IIPs, and is histopathologically identified as usual interstitial pneumonia (UIP). Additional diseases within the IIP category include desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, acute interstitial pneumonia, cryptogenic organizing pneumonia, lymphocytic interstitial pneumonia, and nonspecific interstitial pneumonia (NSIP). IPF carries a poor prognosis, with a mean survival time of less than 5 years after diagnosis (2-5). Biopsies from a single patient can show heterogenous patterns consistent with both UIP and NSIP (4, 6, 7), suggesting that NSIP shares common pathogenic mechanisms with UIP.Diagnoses of patients with IPF who do not exhibit classic high-resolution computed tomography scan changes are confirmed by histopathologic evaluations of surgical lung biopsies, which demonstrate the pattern of UIP. Hallmark features of UIP include epithelial cell hyperplasia, basement membrane denudation, alveolar consolidation, and fibroblastic foci in a pa...

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Aspiration

Burg¹,

Benscoter²

2020

Diagnostic and Interventional Bronchoscopy in Children

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Acid and particulate-induced aspiration lung injury in mice: importance of MCP-1

Abstract: Knight. Acid and particulate-induced aspiration lung injury in mice: importance of MCP-1.

Cited by 60 publications

References 34 publications

Role of Macrophage Chemoattractant Protein-1 in Acute Inflammation after Lung Contusion

Role of Macrophage Chemoattractant Protein-1 in Acute Inflammation after Lung Contusion

Animal Models of Fibrotic Lung Disease

Aspiration

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