scholarly journals Smooth Muscle Hypocontractility and Airway Normoresponsiveness in a Mouse Model of Pulmonary Allergic Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Magali Boucher ◽  
Cyndi Henry ◽  
Alexis Dufour-Mailhot ◽  
Fatemeh Khadangi ◽  
Ynuk Bossé
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Cell ◽  
Allergic Inflammation ◽  
Cell Hyperplasia ◽  
Once Daily ◽  
Dust Mite ◽  
Pulmonary Allergic Inflammation

The contractility of airway smooth muscle (ASM) is labile. Although this feature can greatly modulate the degree of airway responsiveness in vivo, the extent by which ASM’s contractility is affected by pulmonary allergic inflammation has never been compared between strains of mice exhibiting a different susceptibility to develop airway hyperresponsiveness (AHR). Herein, female C57BL/6 and BALB/c mice were treated intranasally with either saline or house dust mite (HDM) once daily for 10 consecutive days to induce pulmonary allergic inflammation. The doses of HDM were twice greater in the less susceptible C57BL/6 strain. All outcomes, including ASM contractility, were measured 24 h after the last HDM exposure. As expected, while BALB/c mice exposed to HDM became hyperresponsive to a nebulized challenge with methacholine in vivo, C57BL/6 mice remained normoresponsive. The lack of AHR in C57BL/6 mice occurred despite exhibiting more than twice as much inflammation than BALB/c mice in bronchoalveolar lavages, as well as similar degrees of inflammatory cell infiltrates within the lung tissue, goblet cell hyperplasia and thickening of the epithelium. There was no enlargement of ASM caused by HDM exposure in either strain. Unexpectedly, however, excised tracheas derived from C57BL/6 mice exposed to HDM demonstrated a decreased contractility in response to both methacholine and potassium chloride, while tracheas from BALB/c mice remained normocontractile following HDM exposure. These results suggest that the lack of AHR in C57BL/6 mice, at least in an acute model of HDM-induced pulmonary allergic inflammation, is due to an acquired ASM hypocontractility.

scholarly journals The Blocking Effect of the Glycoprotein IIb/IIIa Receptor in the Mouse Model of Asthma

2021 ◽  
Author(s):  
Seo-Hee Kim ◽  
Hoang Kim Tu Trinh ◽  
Hae-Sim Park ◽  
Yoo Seob Shin
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Cell ◽  
Critical Role ◽  
Allergic Inflammation ◽  
Positive Control ◽  
Blocking Effect ◽  
Histological Evaluation ◽  
Eosinophilic Inflammation

Abstract Background: It is apparent that the interaction between platelets and eosinophils plays a critical role in the activation of allergic inflammation. We investigated whether blocking of the glycoprotein (GP) IIb/IIIa receptor can attenuate allergic inflammation and airway hyperresponsiveness through inhibition of platelet-eosinophil aggregation (PEA) in asthma.Methods: BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 0 and 14, followed by 3 nebulized OVA challenges on days 28-30. On each challenge day, 5 mg/kg tirofiban was administered intraperitoneally 30 minutes before the challenge. Mice were assessed for airway hyperresponsiveness (AHR), airway inflammation, and the degree of PEA. Finally, the activation levels of platelets and eosinophils were evaluated.Results: Tirofiban treatment decreased AHR and eosinophilic inflammation in BAL fluid. This treatment also reduced the levels of IL-4, IL-5, and IL-13 in BAL fluid and airway inflammatory cell infiltration in histological evaluation. Interestingly, the blocking of the GP IIb/IIIa receptor more reduced PEA in both blood and lung tissue of tirofiban-treated mice than in those of the positive control mice, and both eosinophilic and platelet activations were attenuated in tirofiban-treated mice.Conclusion: The blocking of GP IIb/IIIa receptor with tirofiban can attenuate AHR and airway inflammation through the inhibition of PEA and activation.

scholarly journals The blocking effect of the glycoprotein IIb/IIIa receptor in the mouse model of asthma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Seo-Hee Kim ◽  
Hoang Kim Tu Trinh ◽  
Hae-Sim Park ◽  
Yoo Seob Shin
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Cell ◽  
Critical Role ◽  
Allergic Inflammation ◽  
Positive Control ◽  
Blocking Effect ◽  
Histological Evaluation ◽  
Eosinophilic Inflammation

Abstract Background It is apparent that the interaction between platelets and eosinophils plays a critical role in the activation of allergic inflammation. We investigated whether blocking of the glycoprotein (GP) IIb/IIIa receptor can attenuate allergic inflammation and airway hyperresponsiveness through inhibition of platelet–eosinophil aggregation (PEA) in asthma. Methods BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 0 and 14, followed by 3 nebulized OVA challenges on days 28–30. On each challenge day, 5 mg/kg tirofiban was administered intraperitoneally 30 min before the challenge. Mice were assessed for airway hyperresponsiveness (AHR), airway inflammation, and the degree of PEA. Finally, the activation levels of platelets and eosinophils were evaluated. Results Tirofiban treatment decreased AHR and eosinophilic inflammation in Bronchoalveolar Lavage (BAL) fluid. This treatment also reduced the levels of interleukin (IL)-4, IL-5, and IL-13 in BAL fluid and airway inflammatory cell infiltration in histological evaluation. Interestingly, the blocking of the GP IIb/IIIa receptor more reduced PEA in both blood and lung tissue of tirofiban-treated mice than in those of the positive control mice, and both eosinophilic and platelet activations were attenuated in tirofiban-treated mice. Conclusions The blocking of GP IIb/IIIa receptor with tirofiban can attenuate AHR and airway inflammation through the inhibition of PEA and activation.

scholarly journals Marijuana smoke induces severe pulmonary hyperresponsiveness, inflammation, and emphysema in a predictive mouse model not via CB1 receptor activation

2017 ◽  
Vol 313 (2) ◽  
pp. L267-L277 ◽  
Author(s):  
Z. Helyes ◽  
Á. Kemény ◽  
K. Csekő ◽  
É. Szőke ◽  
K. Elekes ◽  
...  
Keyword(s):  
Tobacco Smoke ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Cell ◽  
Cannabinoid Receptor ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Whole Body ◽  
Myeloperoxidase Activity ◽  
Tissue Destruction ◽  
Cell Hyperplasia

Sporadic clinical reports suggested that marijuana smoking induces spontaneous pneumothorax, but no animal models were available to validate these observations and to study the underlying mechanisms. Therefore, we performed a systematic study in CD1 mice as a predictive animal model and assessed the pathophysiological alterations in response to 4-mo-long whole body marijuana smoke with integrative methodologies in comparison with tobacco smoke. Bronchial responsiveness was measured with unrestrained whole body plethysmography, cell profile in the bronchoalveolar lavage fluid with flow cytometry, myeloperoxidase activity with spectrophotometry, inflammatory cytokines with ELISA, and histopathological alterations with light microscopy. Daily marijuana inhalation evoked severe bronchial hyperreactivity after a week. Characteristic perivascular/peribronchial edema, atelectasis, apical emphysema, and neutrophil and macrophage infiltration developed after 1 mo of marijuana smoking; lymphocyte accumulation after 2 mo; macrophage-like giant cells, irregular or destroyed bronchial mucosa, goblet cell hyperplasia after 3 mo; and severe atelectasis, emphysema, obstructed or damaged bronchioles, and endothelial proliferation at 4 mo. Myeloperoxidase activity, inflammatory cell, and cytokine profile correlated with these changes. Airway hyperresponsiveness and inflammation were not altered in mice lacking the CB1 cannabinoid receptor. In comparison, tobacco smoke induced hyperresponsiveness after 2 mo and significantly later caused inflammatory cell infiltration/activation with only mild emphysema. We provide the first systematic and comparative experimental evidence that marijuana causes severe airway hyperresponsiveness, inflammation, tissue destruction, and emphysema, which are not mediated by the CB1 receptor.

scholarly journals Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs

2002 ◽  
Vol 93 (4) ◽  
pp. 1296-1300 ◽  
Author(s):  
Debra J. Turner ◽  
Peter B. Noble ◽  
Matthew P. Lucas ◽  
Howard W. Mitchell
Keyword(s):  
Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Porcine Model ◽  
Smooth Muscle Contraction ◽  
Airway Wall ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Airway Narrowing

Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural pressures (0–20 cmH2O). Contractile responses to ACh were measured in bronchial segments and in isolated tracheal smooth muscle strips isolated from control and test (ovalbumin sensitized and challenged) pigs. Test airways narrowed less than controls ( P < 0.0001). Test pigs showed reduced contractility to ACh, both in isolated bronchi ( P < 0.01) and smooth muscle strips ( P < 0.01). Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive pigs may be related to decreased smooth muscle contractility. These data suggest that mechanisms external to the airway wall may be important to the hyperresponsive nature of sensitized lungs.

Hyperoxia-induced airway hyperresponsiveness and remodeling in immature rats

1992 ◽  
Vol 262 (3) ◽  
pp. L263-L269 ◽  
Author(s):  
M. B. Hershenson ◽  
S. Aghili ◽  
N. Punjabi ◽  
C. Hernandez ◽  
D. W. Ray ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Muscle Layer ◽  
Airway Responsiveness ◽  
Wall Thickening ◽  
Small Airways ◽  
Smooth Muscle Layer ◽  
Hyperoxic Exposure ◽  
Immature Rats

We exposed 21-day-old rats to either normoxia or hyperoxia (greater than 95% O2) for 8 days and assessed in vivo airway responsiveness to aerosolized and intravenous methacholine (MCh) and airway architecture. Airway responsiveness was determined using a plethysmographic method. Hyperoxia increased airway cholinergic responsiveness, as reflected in a decreased mean ED200 (concentration of MCh required to increase respiratory system resistance by 100%) for both aerosolized MCh [air exposed, 5.94 +/- 2.50 vs. O2 exposed, 0.29 +/- 3.34 (SD) mg/ml, P = 0.0013, unpaired t test] and intravenous MCh (air, 1.40 x 10(-8) vs. O2, 2.45 x 10(-10) mol/kg, P = 0.0002). Airway morphometry was studied in a separate cohort of animals. After fixation by distension with Formalin at 25 cmH2O pressure, each airway cross section was photographed, and airway circumference, epithelial area, and smooth muscle layer area were determined by means of contour tracing using a digitizing pad and microcomputer. For the small airways (circumference less than 1,000 microns), hyperoxia increased both mean epithelial thickness (air, 4.88 +/- 0.53; O2, 8.64 +/- 0.90 microns) and mean smooth muscle layer thickness (air, 2.69 +/- 0.11; O2, 4.79 +/- 0.56 microns; P less than 0.0001 for each). O2 had similar effects on the larger (1,000-3,000 microns) central airways (P less than 0.0001 for both layers). We conclude that chronic hyperoxic exposure induces both airway hyperresponsiveness and airway wall thickening in immature rats.

scholarly journals Effects of Thymus vulgaris L., Cinnamomum verum J.Presl and Cymbopogon nardus (L.) Rendle Essential Oils in the Endotoxin-induced Acute Airway Inflammation Mouse Model

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3553
Author(s):  
Eszter Csikós ◽  
Kata Csekő ◽  
Amir Reza Ashraf ◽  
Ágnes Kemény ◽  
László Kereskai ◽  
...  
Keyword(s):  
Mouse Model ◽  
Essential Oils ◽  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Whole Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Thymus Vulgaris ◽  
Inflammatory Conditions ◽  
Inflammatory Parameters

Thyme (TO), cinnamon (CO), and Ceylon type lemongrass (LO) essential oils (EOs) are commonly used for inhalation. However, their effects and mechanisms on inflammatory processes are not well-documented, and the number of in vivo data that would be important to determine their potential benefits or risks is low. Therefore, we analyzed the chemical composition and investigated the activity of TO, CO, and LO on airway functions and inflammatory parameters in an acute pneumonitis mouse model. The components of commercially available EOs were measured by gas chromatography–mass spectrometry. Airway inflammation was induced by intratracheal endotoxin administration in mice. EOs were inhaled during the experiments. Airway function and hyperresponsiveness were determined by unrestrained whole-body plethysmography on conscious animals. Myeloperoxidase (MPO) activity was measured by spectrophotometry from lung tissue homogenates, from which semiquantitative histopathological scores were assessed. The main components of TO, CO, and LO were thymol, cinnamaldehyde, and citronellal, respectively. We provide here the first evidence that TO and CO reduce inflammatory airway hyperresponsiveness and certain cellular inflammatory parameters, so they can potentially be considered as adjuvant treatments in respiratory inflammatory conditions. In contrast, Ceylon type LO inhalation might have an irritant effect (e.g., increased airway hyperresponsiveness and MPO activity) on the inflamed airways, and therefore should be avoided.

scholarly journals High dose vitamin D3 empowers effects of subcutaneous immunotherapy in a grass pollen-driven mouse model of asthma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Hesse ◽  
N. van Ieperen ◽  
Arjen H. Petersen ◽  
J. N. G. Oude Elberink ◽  
Antoon J. M. van Oosterhout ◽  
...  
Keyword(s):  
Mouse Model ◽  
Grass Pollen ◽  
Airway Hyperresponsiveness ◽  
Allergic Inflammation ◽  
Optimal Dose ◽  
Lavage Fluid ◽  
Subcutaneous Immunotherapy ◽  
High Dose ◽  
Allergen Specific Immunotherapy ◽  
Neutralizing Capacity

AbstractAllergen-specific immunotherapy (AIT) has the potential to provide long-term protection against allergic diseases. However, efficacy of AIT is suboptimal, while application of high doses allergen has safety concerns. The use of adjuvants, like 1,25(OH)2VitD3 (VitD3), can improve efficacy of AIT. We have previously shown that low dose VitD3 can enhance suppression of airway inflammation, but not airway hyperresponsiveness in a grass pollen (GP)-subcutaneous immunotherapy (SCIT) mouse model of allergic asthma. We here aim to determine the optimal dose and formulation of VitD3 for the GP SCIT. GP-sensitized BALBc/ByJ mice received three SCIT injections of VitD3-GP (30, 100, and 300 ng or placebo). Separately, synthetic lipids, SAINT, was added to the VitD3-GP-SCIT formulation (300 nmol) and control groups. Subsequently, mice were challenged with intranasal GP, and airway hyperresponsiveness, GP-specific IgE, -IgG1, and -IgG2a, ear-swelling responses (ESR), eosinophils in broncho-alveolar lavage fluid and lung were measured. VitD3 supplementation of GP-SCIT dose-dependently induced significantly enhanced suppression of spIgE, inflammation and hyperresponsiveness, while neutralizing capacity was improved and ESR were reduced. Addition of VitD3 further decreased Th2 cytokine responses and innate cytokines to allergens in lung tissue by GP-SCIT. However, addition of synthetic lipids to the allergen/VitD3 mixes had no additional effect on VitD3-GP-SCIT. We find a clear, dose dependent effect of VitD3 on GP-SCIT-mediated suppression of allergic inflammation and airway hyperresponsiveness. In contrast, addition of synthetic lipids to the allergen/VitD3 mix had no therapeutic effect. These studies underscore the relevance of VitD3 as an adjuvant to improve clinical efficacy of SCIT treatment regimens.

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