Dynamics of inflammatory cell recruitment in a cigarette smoke induced COPD mouse model

An early event in the pathogenesis of emphysema is the development of inflammation associated with accumulation of polymorphonuclear leukocytes (PMN) in small airways, and inflammatory cell recruitment from the circulation involves migration across endothelial and epithelial cell barriers. Platelet-activating factor (PAF) promotes transendothelial migration in several vascular beds, and we postulated that increased PAF production in the airways of smokers might enhance inflammatory cell recruitment and exacerbate inflammation. To examine this possibility, we incubated human lung microvascular endothelial cells (HMVEC-L) with cigarette smoke extract (CSE) and found that CSE inhibits PAF-acetylhydrolase (PAF-AH) activity. This enhances HMVEC-L PAF production and PMN adherence, and adherence is blocked by PAF receptor antagonists (CV3988 or ginkgolide B). CSE also inhibited PAF-AH activity of lung endothelial cells isolated from wild-type (WT) and iPLA2β knockout mice, and with WT cells, CSE enhanced PAF production and RAW 264.7 cell adherence. In contrast, CSE did not affect PAF production or RAW 264.7 cell adherence to iPLA2β-null cells, suggesting that iPLA2β plays an important role in PAF production by lung endothelial cells. These findings suggest that inhibition of PAF-AH by components of cigarette smoke may initiate or exacerbate inflammatory lung disease by enhancing PAF production and promoting accumulation of inflammatory cells in small airways. In addition, iPLA2β is identified as a potential target for therapeutic interventions to reduce airway inflammation and the progression of chronic lung disease.

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CCR2 and CD44 Promote Inflammatory Cell Recruitment during Fatty Liver Formation in a Lithogenic Diet Fed Mouse Model

PLoS ONE ◽

10.1371/journal.pone.0065247 ◽

2013 ◽

Vol 8 (6) ◽

pp. e65247 ◽

Cited By ~ 15

Author(s):

Charlotte E. Egan ◽

Erin K. Daugherity ◽

Arlin B. Rogers ◽

Delbert S. Abi Abdallah ◽

Eric Y. Denkers ◽

...

Keyword(s):

Mouse Model ◽

Fatty Liver ◽

Inflammatory Cell ◽

Cell Recruitment ◽

Lithogenic Diet ◽

Inflammatory Cell Recruitment

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The composition of cigarette smoke determines inflammatory cell recruitment to the lung in COPD mouse models

Clinical Science ◽

10.1042/cs20130117 ◽

2013 ◽

Vol 126 (3) ◽

pp. 207-221 ◽

Cited By ~ 57

Author(s):

Gerrit John ◽

Katrin Kohse ◽

Jürgen Orasche ◽

Ahmed Reda ◽

Jürgen Schnelle-Kreis ◽

...

Keyword(s):

Inflammatory Response ◽

Cigarette Smoke ◽

Mouse Models ◽

Inflammatory Cell ◽

Biological Effects ◽

Acute Inflammatory Response ◽

Cell Recruitment ◽

Gm Csf ◽

Cell Counts ◽

Inflammatory Cell Recruitment

COPD (chronic obstructive pulmonary disease) is caused by exposure to toxic gases and particles, most often CS (cigarette smoke), leading to emphysema, chronic bronchitis, mucus production and a subsequent decline in lung function. The disease pathogenesis is related to an abnormal CS-induced inflammatory response of the lungs. Similar to active (mainstream) smoking, second hand (sidestream) smoke exposure severely affects respiratory health. These processes can be studied in vivo in models of CS exposure of mice. We compared the acute inflammatory response of female C57BL/6 mice exposed to two concentrations [250 and 500 mg/m3 TPM (total particulate matter)] of sidestream and mainstream CS for 3 days and interpreted the biological effects based on physico-chemical differences in the gas and particulate phase composition of CS. BAL (bronchoalveolar lavage fluid) was obtained to perform differential cell counts and to measure cytokine release. Lung tissue was used to determine mRNA and protein expression of proinflammatory genes and to assess tissue inflammation. A strong acute inflammatory response characterized by neutrophilic influx, increased cytokine secretion [KC (keratinocyte chemoattractant), TNF-α (tumour necrosis factor α), MIP-2 (macrophage inflammatory protein 2), MIP-1α and MCP-1 (monocyte chemoattractant protein-1)], pro-inflammatory gene expression [KC, MIP-2 and MMP12 (matrix metalloproteinase 12)] and up-regulated GM-CSF (granulocyte macrophage colony-stimulating factor) production was observed in the mainstream model. After sidestream exposure there was a dampened inflammatory reaction consisting only of macrophages and diminished GM-CSF levels, most likely caused by elevated CO concentrations. These results demonstrate that the composition of CS determines the dynamics of inflammatory cell recruitment in COPD mouse models. Different initial inflammatory processes might contribute to COPD pathogenesis in significantly varying ways, thereby determining the outcome of the studies.

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Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis

PLoS ONE ◽

10.1371/journal.pone.0145147 ◽

2015 ◽

Vol 10 (12) ◽

pp. e0145147 ◽

Cited By ~ 7

Author(s):

Silvia Affò ◽

Daniel Rodrigo-Torres ◽

Delia Blaya ◽

Oriol Morales-Ibanez ◽

Mar Coll ◽

...

Keyword(s):

Chemokine Receptor ◽

Inflammatory Cell ◽

Liver Inflammation ◽

Cell Recruitment ◽

Inflammatory Cell Recruitment

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The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01098-15 ◽

2015 ◽

Vol 59 (10) ◽

pp. 6317-6327 ◽

Cited By ~ 21

Author(s):

Hussein Traboulsi ◽

Alexandre Cloutier ◽

Kumaraswamy Boyapelly ◽

Marc-André Bonin ◽

Éric Marsault ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Inflammatory Response ◽

Lung Inflammation ◽

Inflammatory Cell ◽

Influenza Virus Infection ◽

Cytokine Gene Expression ◽

Cell Recruitment ◽

Inflammatory Cell Recruitment ◽

Anti Inflammatory

ABSTRACTThe host response to influenza virus infection is characterized by an acute lung inflammatory response in which intense inflammatory cell recruitment, hypercytokinemia, and a high level of oxidative stress are present. The sum of these events contributes to the virus-induced lung damage that leads to high a level of morbidity and mortality in susceptible infected patients. In this context, we identified compounds that can simultaneously reduce the excessive inflammatory response and the viral replication as a strategy to treat influenza virus infection. We investigated the anti-inflammatory and antiviral potential activities of isoliquiritigenin (ILG). Interestingly, we demonstrated that ILG is a potent inhibitor of influenza virus replication in human bronchial epithelial cells (50% effective concentration [EC50] = 24.7 μM). In addition, our results showed that this molecule inhibits the expression of inflammatory cytokines induced after the infection of cells with influenza virus. We demonstrated that the anti-inflammatory activity of ILG in the context of influenza virus infection is dependent on the activation of the peroxisome proliferator-activated receptor gamma pathway. Interestingly, ILG phosphate (ILG-p)-treated mice displayed decreased lung inflammation as depicted by reduced cytokine gene expression and inflammatory cell recruitment. We also demonstrated that influenza virus-specific CD8+effector T cell recruitment was reduced up to 60% in the lungs of mice treated with ILG-p (10 mg/kg) compared to that in saline-treated mice. Finally, we showed that administration of ILG-p reduced lung viral titers and morbidity of mice infected with the PR8/H1N1 virus.

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