Chemokine receptor CXCR3 is important for lung tissue damage and airway remodeling induced by short-term exposure to cigarette smoking in mice

Nie, Lei; Liu, Zhen-jia; Zhou, Weixun; Xiang, Ruo‐Lan; Xiao, Yu; Liu, Bao; Pang, Bao-sen; Gao, Jinming

doi:10.1038/aps.2009.192

Cited by 7 publications

(3 citation statements)

References 35 publications

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“…Interestingly, however, CXCR3-deficient mice have been reported to show reduced collagen deposition and airway remodeling in response to cigarette smoke. 31 Our studies have a number of limitations. First, we used cells from adolescent and adult donors, and studies are needed to examine whether epithelial cells from infants would show enhanced responses to HRV infection.…”

Section: Discussionmentioning

confidence: 94%

Chemokine release from human rhinovirus–infected airway epithelial cells promotes fibroblast migration

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Shariff

Traves

et al. 2016

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 94%

Chemokine release from human rhinovirus–infected airway epithelial cells promotes fibroblast migration

Shelfoon

Shariff

Traves

et al. 2016

Journal of Allergy and Clinical Immunology

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“…The mice were sacrificed and the lungs were removed, inflated to 25 cmH 2 O with 10% formalin and fixed overnight, then embedded in paraffin, and sectioned at 5 μm as described previously [ 16 - 18 ]. Lung sections were stained with hematoxylin & eosin reagent.…”

Section: Methodsmentioning

confidence: 99%

Attenuation of antigen-induced airway hyperresponsiveness and inflammation in CXCR3 knockout mice

et al. 2011

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BackgroundCD8+ T cells participate in airway hyperresponsiveness (AHR) and allergic pulmonary inflammation that are characteristics of asthma. CXCL10 by binding to CXCR3 expressed preferentially on activated CD8+ T cells, attracts T cells homing to the lung. We studied the contribution and limitation of CXCR3 to AHR and airway inflammation induced by ovalbumin (OVA) using CXCR3 knockout (KO) mice.MethodsMice were sensitized and challenged with OVA. Lung histopathological changes, AHR, cellular composition and levels of inflammatory mediators in bronchoalveolar lavage (BAL) fluid, and lungs at mRNA and protein levels, were compared between CXCR3 KO mice and wild type (WT) mice.ResultsCompared with the WT controls, CXCR3 KO mice showed less OVA-induced infiltration of inflammatory cells around airways and vessels, and less mucus production. CXCR3 KO mice failed to develop significant AHR. They also demonstrated significantly fewer CD8+ T and CD4+ T cells in BAL fluid, lower levels of TNFα and IL-4 in lung tissue measured by real-time RT-PCR and in BAL fluid by ELISA, with significant elevation of IFNγ mRNA and protein expression levels.ConclusionsWe conclude that CXCR3 is crucial for AHR and airway inflammation by promoting recruitment of more CD8+ T cells, as well as CD4+ T cells, and initiating release of proinflammatory mediators following OVA sensitization and challenge. CXCR3 may represent a novel therapeutic target for asthma.

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“…Animal models of COPD have begun testing other chemokine receptor antagonists to identify promising candidates. CCR6 and CXCR3 knockout mice displayed reduced lung inflammation and evidence of protection against emphysema, when exposed to cigarette smoke ( 126 , 127 ). Treatment with anti-CCR5 in an emphysema mouse model resulted in the reduction of apoptosis, DNA injury and alveolar remodelling with a subsequent reduction in lung inflammation ( 128 ).…”

Section: Current Strategies To Target Leukocyte Trafficking In Lung Diseasesmentioning

confidence: 99%

New Pharmacological Tools to Target Leukocyte Trafficking in Lung Disease

et al. 2021

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Infection and inflammation of the lung results in the recruitment of non-resident immune cells, including neutrophils, eosinophils and monocytes. This swift response should ensure clearance of the threat and resolution of stimuli which drive inflammation. However, once the threat is subdued this influx of immune cells should be followed by clearance of recruited cells through apoptosis and subsequent efferocytosis, expectoration or retrograde migration back into the circulation. This cycle of cell recruitment, containment of threat and then clearance of immune cells and repair is held in exquisite balance to limit host damage. Advanced age is often associated with detrimental changes to the balance described above. Cellular functions are altered including a reduced ability to traffic accurately towards inflammation, a reduced ability to clear pathogens and sustained inflammation. These changes, seen with age, are heightened in lung disease, and most chronic and acute lung diseases are associated with an exaggerated influx of immune cells, such as neutrophils, to the airways as well as considerable inflammation. Indeed, across many lung diseases, pathogenesis and progression has been associated with the sustained presence of trafficking cells, with examples including chronic diseases such as Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis and acute infections such as Pneumonia and Pneumonitis. In these instances, there is evidence that dysfunctional and sustained recruitment of cells to the airways not only increases host damage but impairs the hosts ability to effectively respond to microbial invasion. Targeting leukocyte migration in these instances, to normalise cellular responses, has therapeutic promise. In this review we discuss the current evidence to support the trafficking cell as an immunotherapeutic target in lung disease, and which potential mechanisms or pathways have shown promise in early drug trials, with a focus on the neutrophil, as the quintessential trafficking immune cell.

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Chemokine receptor CXCR3 is important for lung tissue damage and airway remodeling induced by short-term exposure to cigarette smoking in mice

Cited by 7 publications

References 35 publications

Chemokine release from human rhinovirus–infected airway epithelial cells promotes fibroblast migration

Chemokine release from human rhinovirus–infected airway epithelial cells promotes fibroblast migration

Attenuation of antigen-induced airway hyperresponsiveness and inflammation in CXCR3 knockout mice

New Pharmacological Tools to Target Leukocyte Trafficking in Lung Disease

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