Tiotropium effects on airway inflammatory events in the cat as an animal model for acute cigarette smoke-induced lung inflammation

Shahbazfar, Amir Ali; Tayefi‐Nasrabadi, Hossein; Keyhanmanesh, ‬Rana; Ansarin, Khalil; Ghasemi, Hassan; Rashidi, Amir Hossein; Gosens, Reinoud; Hanifeh, Mohsen

doi:10.3109/01902148.2014.905657

Cited by 17 publications

(13 citation statements)

References 48 publications

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“…Naturally occurring diseases in cats are being increasingly recognized as valid models for human disease that offer various advantages over traditional laboratory animal models [32][33][34][35][36][37][38]. To this end, we are exploring FCGS as a candidate animal model of a variety of human immune-mediated disorders with an oral manifestation (ie, lichen planus, Crohn's disease, graft vs. host disease, and pemphigus vulgaris).…”

Section: Discussionmentioning

confidence: 99%

Feline Foamy Virus Adversely Affects Feline Mesenchymal Stem Cell Culture and Expansion: Implications for Animal Model Development

Arzi

Kol

Murphy

et al. 2015

Stem Cells and Development

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Mesenchymal stem cells (MSCs) are a promising therapeutic option for various immune-mediated and inflammatory disorders due to their potent immunomodulatory and trophic properties. Naturally occurring diseases in large animal species may serve as surrogate animal models of human disease, as they may better reflect the complex genetic, environmental, and physiologic variation present in outbred populations. We work with naturally occurring diseases in large animal species to better understand how MSCs work and to facilitate optimal translation of MSC-based therapies. We are investigating the use of MSC therapy for a chronic oral inflammatory disease in cats. During our efforts to expand fat-derived feline MSCs (fMSCs), we observed that*50% of the cell lines developed giant foamy multinucleated cells in later passages. These morphologic alterations were associated with proliferation arrest. We hypothesized that the cytopathic effects were caused by infection with a retrovirus, feline foamy virus (FFV). Using transmission electron microscopy, polymerase chain reaction, and in vitro assays, we determined that syncytial cell formation and proliferation arrest in fMSCs were caused by FFV strains that were highly homologous to previously reported FFV strains. We determined that the antiretroviral drug, tenofovir, may be used to support ex vivo expansion and salvage of FFV-infected fMSC lines. MSC lines derived from specific pathogen-free cats do not appear to be infected with FFV and may be a source of allogeneic fMSCs for clinical application. FFV infection of fMSC lines may hinder large-scale expansion of autologous MSC for therapeutic use in feline patients.

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Section: Discussionmentioning

confidence: 99%

Feline Foamy Virus Adversely Affects Feline Mesenchymal Stem Cell Culture and Expansion: Implications for Animal Model Development

Arzi

Kol

Murphy

et al. 2015

Stem Cells and Development

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“…Maternal administration of the anti-oxidant n-acetylcysteine protected rat fetal lungs from oxidative damage and prevented the smoke exposure-related decline in glutathione levels 41 . In a feline cigarette exposure model, tiotropium administration was associated with reduction in serum, lung, and tracheal lipid peroxides and abrogated reductions in antioxidant levels 42 . Tiotropium may increase anti-inflammatory signaling through modification of histone deacetylases (HDAC) and modulation of nitric oxide production 43 .…”

Section: Discussionmentioning

confidence: 90%

The relationship between plasma lipid peroxidation products and primary graft dysfunction after lung transplantation is modified by donor smoking and reperfusion hyperoxia

Diamond

Porteous

Roberts

et al. 2016

The Journal of Heart and Lung Transplantation

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Purpose Donor smoking history and higher FiO2 at reperfusion are associated with primary graft dysfunction (PGD) after lung transplantation. We hypothesized that oxidative injury biomarkers would be elevated in PGD, with higher levels associated with donor exposure to cigarette smoke and recipient hyperoxia at reperfusion. Methods We performed a nested case control study of 72 lung transplant recipients from the Lung Transplant Outcomes Group cohort. F2-isoprostanes and isofurans were measured by mass spectroscopy in plasma collected after transplantation. Cases were defined in two ways: grade 3 PGD present at day 2 or day 3 after reperfusion (severe PGD), or any grade 3 PGD (any PGD). Results There were 31 severe PGD cases with 41 controls and 35 any PGD cases with 37 controls. Plasma F2-isoprostane levels were higher in severe PGD compared to controls (28.6 pg/ml vs. 19.8 pg/ml, p=0.03). Plasma F2-isoprostane levels were higher in severe PGD compared to controls (29.6 pg/ml vs. 19.0 pg/ml, p=0.03) among patients reperfused with FiO2>40%. Among recipients of lungs from donors with smoke exposure, plasma F2-isoprostane (38.2 pg/ml vs. 22.5 pg/ml, p=0.046) and isofuran (66.9 pg/ml vs. 34.6 pg/ml, p=0.046) levels were higher in severe PGD compared with controls. Conclusions Plasma levels of lipid peroxidation products are higher in patients with severe PGD, in recipients of lungs from donors with smoke exposure, and recipients exposed to higher FiO2 at reperfusion. Oxidative injury is an important mechanism of PGD and may be magnified by donor exposure to cigarette smoke and hyperoxia at reperfusion.

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“…Increased numbers of neutrophils and macrophages in respiratory samples in parallel with exaggerated AHR had been observed in both asthmatic smokers and tobacco smoke-treated cats. 33 , 34 Altered behavior of AMs is a key feature of COPD. 3 Increased numbers of AMs had been observed in lung parenchyma, BAL fluid, and sputum in COPD.…”

Section: Discussionmentioning

confidence: 99%

Increased matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio in smokers with airway hyperresponsiveness and accelerated lung function decline

Lo¹,

Huang²,

He³

et al. 2018

COPD

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BackgroundAirway hyperresponsiveness (AHR) is associated with airway inflammation and a rapid decline in lung function and is a predictor of future risk of COPD among smokers. Alveolar macrophages (AMs) from patients with COPD release a greater amount of matrix metalloproteinase (MMP)-9. We hypothesized that the imbalance between MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) is related to AHR in smokers.Patients and methodsHealthy smokers with AHR (AHR + S) or smokers without AHR (AHR − S; divided according to a methacholine challenge test) and nonsmokers without AHR (AHR − NS) were enrolled. Spirometry was performed during enrollment and repeated after 5 years. Initially, AMs recovered from bronchoalveolar lavage (BAL) fluid were cultured in the presence of p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580), MAPK kinase (MEK) 1/2 (the MEK of extracellular signal-regulated kinase [ERK] inhibitor, PD98059), or medium alone for 24 h. The release of MMP-9 and TIMP-1 in culture supernatants was measured by enzyme-linked immunosorbent assay.ResultsA greater reduction in forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), FEV1 (as a percentage of the predicted value [%pred]), and maximal mid-expiratory flow (MMEF) was observed among AHR + S in the 5-year period. There was a higher proportion of neutrophils and a lower proportion of AMs in BAL fluid recovered from AHR + S. Compared to AMs from AHR − NS and AHR − S, AMs from nonsmokers with AHR (AHR + NS) released more MMP-9 and less TIMP-1, with an increase in MMP-9/TIMP-1 ratios. The MMP-9/TIMP-1 ratio in smokers was positively correlated with the annual decline in FEV1%pred, FVC%pred, and MMEF%pred. Both SB203580 and PD98059 significantly reduced MMP-9, but not TIMP-1, from AMs of smokers.ConclusionAMs of AHR + NS produce excessive MMP-9 over TIMP-1, which may be a predictor of the development of airway obstruction. Inhibition of p38 MAPK and ERK suppresses the generation of MMP-9 by AMs from smokers.

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Tiotropium effects on airway inflammatory events in the cat as an animal model for acute cigarette smoke-induced lung inflammation

Abstract: Cigarette smoke increases airway responsiveness and inflammation in a cat model of CS induced lung inflammation. It can effectively be reduced by treatment with tiotropium.

Cited by 17 publications

References 48 publications

Feline Foamy Virus Adversely Affects Feline Mesenchymal Stem Cell Culture and Expansion: Implications for Animal Model Development

Feline Foamy Virus Adversely Affects Feline Mesenchymal Stem Cell Culture and Expansion: Implications for Animal Model Development

The relationship between plasma lipid peroxidation products and primary graft dysfunction after lung transplantation is modified by donor smoking and reperfusion hyperoxia

Increased matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1 ratio in smokers with airway hyperresponsiveness and accelerated lung function decline

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