Genetic variation associates with susceptibility for cigarette smoke-induced neutrophilia in mice

Pouwels, Simon D.; Heijink, Irene H.; Brouwer, Uilke; Gras, R.; Boef, Lisette E. den; Boezen, H. Marike; Korstanje, Ron; Oosterhout, Antoon J. M. van; Nawijn, Martijn C.

doi:10.1152/ajplung.00118.2014

Cited by 16 publications

(18 citation statements)

References 56 publications

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“…Thus, the risk among smokers to develop smoking-related disease might be associated with specific SNPs that are related to immune function. [29][30][31] In conclusion, our investigation suggests that genetic variation at SNPs sequences might predict the risk of smoking-related disease. Thus, using SNPs as a predictive biomarker of individual risk or as additional motivation for smoking cessation merit further investigation.…”

Section: Discussionmentioning

confidence: 59%

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Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals

Luetragoon

Rutqvist²,

Tangvarasittichai

et al. 2018

Immunology

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Cigarette smoke contains toxic and carcinogenic substances that contribute to the development of cancer and various diseases. Genetic variation might be important, because not all smokers develop smoking-related disease. The current study addressed the possible interactions among selected single nucleotide polymorphisms (SNPs) in genes related to systemic inflammation, smoking status, the levels of circulating immune response cells and plasma biomarkers of systemic inflammation. Sixty-four healthy blood donors were recruited, 31 of whom were current smokers and 33 were never-users of tobacco products, references. Compared to references, the smokers showed significantly increased levels of circulating total white blood cells, lymphocytes, monocytes, neutrophils, basophils and C-reactive protein (CRP). Smokers also more frequently exhibited circulating cell phenotypes that are associated with an immunocompromised state: CD8 cells in the lymphocyte group, CD13 CD11 , CD13 CD14 , CD13 CD56 cells in the monocyte group and CD13 CD11 , CD13 CD56 cells in the neutrophil group. We observed an interaction among SNPs, smoking status and some of the studied biomarkers. The average plasma CRP level was significantly higher among the smokers, with the highest level found among those with the CRP rs1800947 CC genotype. Additionally, an increased CD8 GZB cells in the CD8 group were found among smokers with the GZB rs8192917 AA genotype. Thus, smoking appears to be associated with systemic inflammation and increased levels of circulating immunosuppressive cells. The extent of these effects was associated with SNPs among the smokers. This observation may contribute to a better understanding of the genetic susceptibility of smoking-related disease and the variations observed in clinical outcomes.

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Section: Discussionmentioning

confidence: 59%

“…The effect of smoking was more pronounced among individuals exhibiting the studied SNPs, and was not observed for all smokers. Thus, the risk among smokers to develop smoking‐ related disease might be associated with specific SNPs that are related to immune function …”

Section: Discussionmentioning

confidence: 99%

Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals

Luetragoon

Rutqvist²,

Tangvarasittichai

et al. 2018

Immunology

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“…The mouse model of smoke-induced emphysema exhibits variable levels of infiltrating neutrophils depending on the mouse strain (37), and rarely exhibits neutrophil elastase activity in the BAL. The rabbit model presented in this study exhibits statistically significant increases in tissue neutrophils at 16 weeks of smoke exposure.…”

Section: Discussionmentioning

confidence: 99%

Single-Photon Emission Computed Tomography/Computed Tomography Imaging in a Rabbit Model of Emphysema Reveals Ongoing Apoptosis In Vivo

Goldklang¹,

Tekabe²,

Zelonina³

et al. 2016

Am J Respir Cell Mol Biol

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Evaluation of lung disease is limited by the inability to visualize ongoing pathological processes. Molecular imaging that targets cellular processes related to disease pathogenesis has the potential to assess disease activity over time to allow intervention before lung destruction. Because apoptosis is a critical component of lung damage in emphysema, a functional imaging approach was taken to determine if targeting apoptosis in a smoke exposure model would allow the quantification of early lung damage in vivo. Rabbits were exposed to cigarette smoke for 4 or 16 weeks and underwent single-photon emission computed tomography/computed tomography scanning using technetium99m-rhAnnexin V-128. Imaging results were correlated with ex vivo tissue analysis to validate the presence of lung destruction and apoptosis. Lung computed tomography scans of long-term smoke-exposed rabbits exhibit anatomical similarities to human emphysema, with increased lung volumes compared with controls. Morphometry on lung tissue confirmed increased mean linear intercept and destructive index at 16 weeks of smoke exposure and compliance measurements documented physiological changes of emphysema. Tissue and lavage analysis displayed the hallmarks of smoke exposure, including increased tissue cellularity and protease activity. Technetium99m-rhAnnexin V-128 single-photon emission computed tomography signal was increased after smoke exposure at 4 and 16 weeks, with confirmation of increased apoptosis through terminal deoxynucleotidyl transferase dUTP nick end labeling staining and increased tissue neutral sphingomyelinase activity in the tissue. These studies not only describe a novel emphysema model for use with future therapeutic applications, but, most importantly, also characterize a promising imaging modality that identifies ongoing destructive cellular processes within the lung.

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“…Independent from etiological point of view, cell death will release autologous antigens that provoke local and systemic host immune response [33]. Long-term exposures to these autologous antigens will upregulated inflammatory biomarkers, and this seems to be correlated with specific SNP sequence and not random events [26, 47]. …”

Section: Inflammation Snps and Clinical Outcome Of Handn Cancer Patientsmentioning

confidence: 99%

The use of rapid and cost-effective blood-based biomarkers in combination with tumour TNM stage for individual head and neck cancer patient treatment selection

Lewin

Andersson

et al. 2017

Med Oncol

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Head and neck (H&N) cancer is an aggressive disease and the incidence has increased in younger population worldwide. Tumour TNM staging is the main basis for treatment decision despite significant variation in clinical outcome. Survival time of these patients has marginally improved during the last 30 years. Various biomarkers with cumbersome analysis, high cost, time consumption and requirement of special laboratory facilities have been investigated. However, none of these biomarkers have been shown to be suitable to use for individual H&N cancer patient treatment selection in the clinic. For practical use in clinical settings, the given biomarkers must be simple to analyse, rapid, cost effective and available in routine laboratories. With this intension, we suggested the combination of standard TNM staging and biomarkers associated with inflammation such as neutrophils, neutrophil to lymphocyte ratio, plasma C-reactive protein or plasma tumour necrosis factor alpha (TNFa) and single-nucleotide polymorphism in TNFa rs1800629 using blood-based analysis. The optimal treatment outcome of H&N cancer by using combination of TNM stage and these blood-based biomarkers for individual patient selection need further investigation.

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Genetic variation associates with susceptibility for cigarette smoke-induced neutrophilia in mice

Abstract: Pouwels SD, Heijink IH, Brouwer U, Gras R, den Boef LE, Boezen HM, Korstanje R, van Oosterhout AJ, Nawijn MC. Genetic variation associates with susceptibility for cigarette smoke-induced neutrophilia in mice.

Cited by 16 publications

References 56 publications

Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals

Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals

Single-Photon Emission Computed Tomography/Computed Tomography Imaging in a Rabbit Model of Emphysema Reveals Ongoing Apoptosis In Vivo

The use of rapid and cost-effective blood-based biomarkers in combination with tumour TNM stage for individual head and neck cancer patient treatment selection

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