Longitudinal characterization of a model of chronic allergic lung inflammation in mice using imaging, functional and immunological methods

2013 ◽  
Vol 125 (12) ◽  
pp. 555-564 ◽  
Author(s):  
Kumar Changani ◽  
Catherine Pereira ◽  
Simon Young ◽  
Robert Shaw ◽  
Simon P. Campbell ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Lung Inflammation ◽  
Allergic Inflammation ◽  
Treated Group ◽  
Similar Rate ◽  
Immunological Methods ◽  
Tissue Density ◽  
Cell Counts ◽  
Rate Of Increase ◽  
Tissue Changes

The present study investigated the role that imaging could have for assessing lung inflammation in a mouse model of HDM (house dust mite)-provoked allergic inflammation. Inflammation is usually assessed using terminal procedures such as BAL (bronchoalveolar lavage) and histopathology; however, MRI (magnetic resonance imaging) and CT (computed tomography) methods have the potential to allow longitudinal, repeated study of individual animals. Female BALB/c mice were administered daily either saline, or a solution of mixed HDM proteins sufficient to deliver a dose of 12 or 25 μg total HDM protein±budesonide (1 mg/kg of body weight, during weeks 5–7) for 7 weeks. AHR (airway hyper-responsiveness) and IgE measurements were taken on weeks 3, 5 and 7. Following imaging sessions at weeks 3, 5 and 7 lungs were prepared for histology. BAL samples were taken at week 7 and lungs prepared for histology. MRI showed a gradual weekly increase in LTI (lung tissue intensity) in animals treated with HDM compared with control. The 25 μg HDM group showed a continual significant increase in LTI between weeks 3 and 7, the 12 μg HDM-treated group showed a similar rate of increase, and plateaued by week 5. A corresponding increase in AHR, cell counts and IgE were observed. CT showed significant increases in lung tissue density from week 1 of HDM exposure and this was maintained throughout the 7 weeks. Budesonide treatment reversed the increase in tissue density. MRI and CT therefore provide non-invasive sensitive methods for longitudinally assessing lung inflammation. Lung tissue changes could be compared directly with the classical functional and inflammatory readouts, allowing more accurate assessments to be made within each animal and providing a clinically translatable approach.

scholarly journals Selective deletion of SHIP-1 in hematopoietic cells in mice leads to severe lung inflammation involving ILC2 cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xujun Ye ◽  
Fengrui Zhang ◽  
Li Zhou ◽  
Yadong Wei ◽  
Li Zhang ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Airway Remodeling ◽  
Pulmonary Inflammation ◽  
Hematopoietic Cells ◽  
Cell Lineage ◽  
Allergic Inflammation ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Whole Body

AbstractSrc homology 2 domain–containing inositol 5-phosphatase 1 (SHIP-1) regulates the intracellular levels of phosphotidylinositol-3, 4, 5-trisphosphate, a phosphoinositide 3–kinase (PI3K) product. Emerging evidence suggests that the PI3K pathway is involved in allergic inflammation in the lung. Germline or induced whole-body deletion of SHIP-1 in mice led to spontaneous type 2-dominated pulmonary inflammation, demonstrating that SHIP-1 is essential for lung homeostasis. However, the mechanisms by which SHIP-1 regulates lung inflammation and the responsible cell types are still unclear. Deletion of SHIP-1 selectively in B cells, T cells, dendritic cells (DC) or macrophages did not lead to spontaneous allergic inflammation in mice, suggesting that innate immune cells, particularly group 2 innate lymphoid cells (ILC2 cells) may play an important role in this process. We tested this idea using mice with deletion of SHIP-1 in the hematopoietic cell lineage and examined the changes in ILC2 cells. Conditional deletion of SHIP-1 in hematopoietic cells in Tek-Cre/SHIP-1 mice resulted in spontaneous pulmonary inflammation with features of type 2 immune responses and airway remodeling like those seen in mice with global deletion of SHIP-1. Furthermore, when compared to wild-type control mice, Tek-Cre/SHIP-1 mice displayed a significant increase in the number of IL-5/IL-13 producing ILC2 cells in the lung at baseline and after stimulation by allergen Papain. These findings provide some hints that PI3K signaling may play a role in ILC2 cell development at baseline and in response to allergen stimulation. SHIP-1 is required for maintaining lung homeostasis potentially by restraining ILC2 cells and type 2 inflammation.

Enhanced Infiltration of Central Memory T Cells to the Lung Tissue during Allergic Lung Inflammation

2021 ◽  
pp. 1-15
Author(s):  
Mashael Alabed ◽  
Asma Sultana Shaik ◽  
Narjes Saheb Sharif-Askari ◽  
Fatemeh Saheb Sharif-Askari ◽  
Shirin Hafezi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lung Tissue ◽  
Lung Inflammation ◽  
Inflammatory Responses ◽  
Memory T Cells ◽  
Central Memory ◽  
Effector Memory ◽  
Differential Distribution ◽  
Allergic Lung Inflammation

Memory T cells play a central role in regulating inflammatory responses during asthma. However, tissue distribution of effector memory (T<sub>EM</sub>) and central memory (T<sub>CM</sub>) T-cell subtypes, their differentiation, and their contribution to the persistence of lung tissue inflammation during asthma are not well understood. Interestingly, an increase in survival and persistence of memory T cells was reported in asthmatic lungs, which may suggest a shift toward the more persistent T<sub>CM</sub> phenotype. In this report, we investigated the differential distribution of memory T-cell subtypes during allergic lung inflammation and the mechanism regulating that. Using an OVA-sensitized asthma mouse model, we observed a significant increase in the frequency of T<sub>CM</sub> cells in inflamed lungs compared to healthy controls. Interestingly, adoptive transfer techniques confirmed substantial infiltration of T<sub>CM</sub> cells to lung tissues during allergic airway inflammation. Expression levels of T<sub>CM</sub> homing receptors, CD34 and GlyCAM-1, were also significantly upregulated in the lung tissues of OVA-sensitized mice, which may facilitate the increased T<sub>CM</sub> infiltration into inflamed lungs. Moreover, a substantial increase in the relative expression of T<sub>CM</sub> profile-associated genes (EOMES, BCL-6, ID3, TCF-7, BCL-2, BIM, and BMI-1) was noted for T<sub>EM</sub> cells during lung inflammation, suggesting a shift for T<sub>EM</sub> into the T<sub>CM</sub> state. To our knowledge, this is the first study to report an increased infiltration of T<sub>CM</sub> cells into inflamed lung tissues and to suggest differentiation of T<sub>EM</sub> to T<sub>CM</sub> cells in these tissues. Therapeutic interference at T<sub>CM</sub> infiltration or differentiations could constitute an alternative treatment approach for lung inflammation.

scholarly journals IL-18 binding protein (IL-18BP) as a novel radiation countermeasure after radiation exposure in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xianghong Li ◽  
Wanchang Cui ◽  
Lisa Hull ◽  
Li Wang ◽  
Tianzheng Yu ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Tissue Damage ◽  
Inflammatory Responses ◽  
Binding Protein ◽  
Treated Group ◽  
Therapeutic Window ◽  
Mouse Serum ◽  
Mouse Heart ◽  
Cell Counts ◽  
Radiation Induced

Abstract Recent studies suggested that radiation exposure causes local and systemic inflammatory responses and induces cell and tissue damage. We have reported that IL-18 plays an important role in radiation-induced injury. Here, we demonstrate that IL-18 binding protein (IL-18BP), a natural antagonist of IL-18, was significantly increased (1.7–63 fold) in mouse serum on day 1 after 0.5–10 Gy TBI. However, this high level of IL-18BP was not sufficient to neutralize the active IL-18 in irradiated mice, resulting in a radiation dose-dependent free IL-18 increase in these mice’s serum which led to pathological alterations to the irradiated cells and tissues and finally caused animal death. Administration of recombinant human (rh) IL-18BP (1.5 mg/kg) with single (24, 48 or 72 h post-TBI) or double doses (48 h and 5 days post-TBI) subcutaneous (SC) injection increased 30-day survival of CD2F1 mice after 9 Gy TBI 12.5–25% compared with the vehicle control treated group, respectively. Furthermore, the mitigative effects of rhIL-18BP included balancing the ratio of IL-18/IL-18BP and decreasing the free IL-18 levels in irradiated mouse serum and significantly increasing blood cell counts, BM hematopoietic cellularity and stem and progenitor cell clonogenicity in mouse BM. Furthermore, IL-18BP treatment inhibited the IL-18 downstream target interferon (IFN)-γ expression in mouse BM, decreased reactive oxygen species (ROS) level in the irradiated mouse heart tissues, attenuated the stress responsive factor GDF-15 (growth differentiation factor-15) and increased the intestine protector citrulline level in total body irradiated mouse serum, implicating that IL-18BP may protect multiple organs from radiation-induced inflammation and oxidative stress. Our data suggest that IL-18 plays a key role in radiation-induced cell and tissue damage and dysfunction; and for the first time demonstrated that IL-18BP counters IL-18 activation and therefore may mitigate/treat radiation-induced multiple organ injuries and increase animal survival with a wider therapeutic window from 24 h and beyond after lethal doses of radiation exposure.

Recombinant human superoxide dismutase reduces lung injury caused by inhaled nitric oxide and hyperoxia

1997 ◽  
Vol 272 (5) ◽  
pp. L903-L907 ◽  
Author(s):  
C. G. Robbins ◽  
S. Horowitz ◽  
T. A. Merritt ◽  
A. Kheiter ◽  
J. Tierney ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Pulmonary Inflammation ◽  
Inhaled Nitric Oxide ◽  
Newborn Piglets ◽  
Markers Of Inflammation ◽  
Cell Counts

We previously demonstrated that 48 h of 100 ppm inhaled nitric oxide (NO) and 90% O2 causes surfactant dysfunction and pulmonary inflammation in mechanically ventilated newborn piglets. Because peroxynitrite (the product of NO and superoxide) is thought to play a major role in the injury process, recombinant human superoxide dismutase (rhSOD, a scavenger of superoxide) might minimize this insult. Four groups of newborn piglets (1-3 days of age) were ventilated with 100 ppm NO and 90% O2 for 48 h. Piglets received no drug, 5 mg/kg rhSOD intratracheally at time 0, 5 mg/kg rhSOD intratracheally at 0 and 24 h, or 10 mg/kg rhSOD by nebulization at time 0. At 48 h, bronchoalveolar lavage (BAL) was performed, and lung tissue was analyzed for markers of inflammation, oxidative injury, acute lung injury, and surfactant function. There were significant differences between rhSOD-treated piglets and untreated controls with respect to BAL neutrophil chemotactic activity, cell counts, and protein concentration as well as lung tissue malondialdehyde concentrations. Minimum surface tension of BAL surfactant from all groups studied was increased, with no differences found among groups. These data suggest that rhSOD, at the doses used, mitigated the inflammatory changes, oxidative damage, and acute lung injury from exposure to 100 ppm NO and 90% O2 but did not appear to improve surfactant function. This has important clinical implications for infants treated with hyperoxia and NO for neonatal lung disorders.

scholarly journals Effective lung-targeted RNAi in mice with peptide-based delivery of nucleic acid

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kaido Kurrikoff ◽  
Krista Freimann ◽  
Kadi-Liis Veiman ◽  
Elin Madli Peets ◽  
Andres Piirsoo ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nucleic Acid ◽  
Lung Disease ◽  
Lung Tissue ◽  
Lung Inflammation ◽  
Disease Models ◽  
Nucleic Acid Delivery ◽  
Acute Lung Inflammation ◽  
Disease Symptoms ◽  
Targeted Gene Therapy

AbstractWe have previously developed efficient peptide-based nucleic acid delivery vectors PF14 and NF55, where we have shown that these vectors preferentially transfect lung tissue upon systemic administration with the nucleic acid. In the current work, we have explored the utilization and potential of these vectors for the lung-targeted gene therapy. Accordingly, we assessed the efficacy of these peptides in (i) two different lung disease models – acute lung inflammation and asthma in mice and (ii) using two different nucleic acid cargos – siRNA and pDNA encoding shRNA. Using RNAi against cytokine TNFα, we showed efficient anti-inflammatory effects in both disease models and observed decreased disease symptoms. Our results highlight the potential of our transfection vectors for lung gene therapy.

Diagnosis of Ventilator-associated Pneumonia 

1997 ◽  
Vol 87 (2) ◽  
pp. 268-276 ◽  
Author(s):  
Laurent Papazian ◽  
Amapola Autillo-Touati ◽  
Pascal Thomas ◽  
Fabienne Bregeon ◽  
Louise Garbe ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Bronchoalveolar Lavage ◽  
Lung Tissue ◽  
Sampling Technique ◽  
Sampling Techniques ◽  
Ventilator Associated Pneumonia ◽  
Direct Examination ◽  
Gram Staining ◽  
Cell Counts ◽  
Sampling Procedures

Background Ventilator-associated pneumonia (VAP) requires early diagnosis and adequate antibiotic therapy. The aim of this prospective postmortem study was to assess the accuracy of direct examination and quantification of intracellular organisms (ICO) for the diagnosis of VAP. Methods Total and differential cell counts were performed on fluids recovered using nonbronchoscopic sampling techniques (blind bronchial sampling [BBS], mini-bronchoalveolar lavage [mini-BAL]) and from bronchoalveolar lavage (BAL) performed during fiberscopy. These 3 sampling techniques were done within 15 min of death without discontinuing mechanical ventilation. Quantification of ICO was performed on each sample recovered from the various sampling procedures. Gram reaction and morphology of bacteria were evaluated on Gram smears. Results The results of each technique were compared with histology and culture of lung tissue specimens obtained by surgical pneumonectomies in 28 patients who died after at least 72 h of mechanical ventilation. Histology was positive in 13 patients and negative in 15 patients. When only VAP with positive lung culture was considered (histologic signs of bronchopneumonia plus positive lung tissue culture), the sensitivity of Gram staining on BAL, mini-BAL, and BBS was 56%, 44%, and 56%, respectively. If all samples were considered, the sensitivity and the specificity of the determination of the percentage of ICO were low (less than 70%) whatever the sampling technique. Conclusions For initial therapeutic guidance, direct examination and presence of ICO do not contribute for establishing the diagnosis of VAP, essentially because of a lack of sensitivity. However, when positive, Gram staining can obviously guide initial antibiotherapy.

The air cysts and cystoid changes in pulmonary tissue

2020 ◽  
Vol 29 (6) ◽  
pp. 745-754
Author(s):  
M. A. Karnaushkina ◽  
D. V. Burenchev ◽  
A. D. Strutynskaya
Keyword(s):  
Lung Tissue ◽  
Clinical Symptoms ◽  
Lung Parenchyma ◽  
Diagnostic Methods ◽  
Pulmonary Tissue ◽  
Clinical Observations ◽  
Bronchopulmonary Diseases ◽  
Tissue Changes ◽  
Radiological Pattern ◽  
Radiological Patterns

Computed tomography (CT) of chest organs is one of the most accurate diagnostic methods allowing the physician to assess the condition of lung parenchyma. Correct interpretation of CT results requires the clinician to recognize normal appearance of lung parenchyma on X-ray and know changes visualized in various bronchopulmonary diseases. It is important that the physician knows and understands underlying cause of a particular radiological pattern in order to discuss with the radiologist lung tissue changes that have been identified considering clinical symptoms. Descriptions of radiological patterns and discussion of corresponding typical clinical observations are presented in the article devoted to air cyst syndrome and cystoid changes in the lung tissue.

Hyperplastic effects of aerosolized sodium metabisulfite on rat airway mucus-secretory epithelial cells

1994 ◽  
Vol 72 (9) ◽  
pp. 1025-1030 ◽  
Author(s):  
Douglas J. Pon ◽  
Carlo J. van Staden ◽  
Louise Boulet ◽  
Ian W. Rodger
Keyword(s):  
Animal Models ◽  
Epithelial Cells ◽  
Bronchoalveolar Lavage ◽  
Lung Tissue ◽  
Small Animal ◽  
Sodium Metabisulfite ◽  
Airway Epithelia ◽  
Tissue Changes ◽  
Small Animal Models ◽  
Ultrasonic Humidifier

The ability of aerosolized sodium metabisulfite to induce hypertrophic and hyperplastic changes in rat airway secretory epithelial cells was investigated. A 10% solution of sodium metabisulfite was aerosolized into a Plexiglas exposure chamber, using an ultrasonic humidifier. The level of SO2 gas generated by this apparatus was measured to be 500 ppm. Measured levels of neutral and acidic mucous glycoproteins in extracts from tracheal and lung tissue were used as indices of hypertrophic (increases in mucus content per cell) and hyperplastic (increased numbers of cells containing mucus per gram of tissue) changes occurring in mucus-secreting cells of the airways. Exposing rats to sodium metabisulfite for 3 weeks resulted in profound increases in total neutral mucous glycoproteins found in tracheal and lung tissue (6.2-fold and 10.1-fold, respectively), compared with the H2O-treated counterparts. Total acidic mucous glycoproteins were significantly elevated in lung tissue only (13.5-fold). In addition, neutral and acidic mucous glycoproteins were elevated 20-fold and 9-fold, respectively, in bronchoalveolar lavage samples prepared from sodium metabisulfite exposed animals. These results indicate that aerosolized sodium metabisulfite may be a useful agent for developing small animal models of mucus hypersecretion.Key words: mucus, hypertrophy, hyperplasia, secretion, airway, epithelia.

Effects Of RHO Kinase Inhibition On Airway And Lung Tissue Mechanics In Animals With Chronic Allergic Inflammation

2011 ◽  
Author(s):  
Patricia A. Silva ◽  
Renato F. Righetti ◽  
Samantha S. Possa ◽  
Rafael A. Reis ◽  
Beatriz M. Saraiva ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Rho Kinase ◽  
Allergic Inflammation ◽  
Tissue Mechanics ◽  
Kinase Inhibition

Skeletal, Dental and Soft Tissue Changes in Postural Class III Malocclusion Treated with a Maxillary Removable Appliance

2007 ◽  
Vol 31 (2) ◽  
pp. 149-152
Author(s):  
Elham Abu Alhaija
Keyword(s):  
Soft Tissue ◽  
Treated Patient ◽  
Treated Group ◽  
T Test ◽  
Class Iii ◽  
Class Iii Malocclusion ◽  
Soft Tissue Profile ◽  
Tissue Changes ◽  
Soft Tissue Changes ◽  
Removable Appliance

Objective: This longitudinal retrospective cephalometric study was undertaken in an attempt to evaluate the effect of upper removable appliances on the hard and soft tissue structures in subjects with postural Class III. Methods: The material consisted of cephalometric films of 17 Class III patients (8 females and 9 males, with a mean age of 10.10 ± 1.63). Each treated patient was matched before treatment with Class III subject for sex and age. Differences in treated group at T1 and T2 and between treated and untreated groups were examined using paired t-test and independent t-test respectively. Results: Treated and untreated Class III subjects differed in mandibular prognathism (SNB, P&lt;0.01). Upper incisors proclined and inter-incisal angle reduced during treatment (P&lt;0.001). Soft tissue A point moved anteriorly as maxillary incisors were proclined (P&lt;0.05). Soft tissue profile was improved (NNP, P&lt;0.05; NAP, P&lt;0.01). Conclusion: Skeletal, dental and soft tissue changes were found in patients treated by upper removable appliance in postural Class III patients. Clinical relevance: upper removable appliance is an efficient method to procline upper incisors in postural Class III malocclusion and may be of greater influence in improving soft tissue profile.

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