scholarly journals Functional and pathological effects of prolonged hyperoxia in neonatal mice

1998 ◽  
Vol 275 (1) ◽  
pp. L110-L117 ◽  
Author(s):  
Barbara B. Warner ◽  
Lorie A. Stuart ◽  
Richard A. Papes ◽  
Jonathan R. Wispé
Keyword(s):  
Cell Proliferation ◽  
Lung Tissue ◽  
Prolonged Exposure ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Functional Changes ◽  
Neonatal Mice ◽  
Fluid Analysis ◽  
Neonatal Hyperoxia

Bronchopulmonary dysplasia (BPD) commonly develops in premature infants. An improved understanding of the pathophysiology of BPD requires better models. In this study, neonatal FVB/N mice were exposed to room air or 85% oxygen for 28 days. Neonatal hyperoxia resulted in decreased alveolar septation, increased terminal air space size, and increased lung fibrosis. These changes were evident after 7 days and more pronounced by 28 days. Decreased alveolarization was preceded by decreased proliferation of lung cells. After 3 days of hyperoxia, cell proliferation was decreased compared with room air littermates. Cell proliferation continued to be decreased in the first 2 wk but normalized by 4 wk. Hyperoxia caused an increased number of inflammatory cells in lung tissue and in lung lavage fluid. Analysis of lung tissue RNA by RT-PCR showed that hyperoxia increased expression of the proinflammatory cytokines interleukin-1α and macrophage inflammatory protein-1α. Prolonged neonatal hyperoxia caused functional changes, decreasing lung volume and pulmonary compliance. We conclude that prolonged exposure of neonatal mice to hyperoxia creates a lesion that is very similar to human BPD and suggests that altered cell proliferation may be important in the pathogenesis of chronic neonatal lung disease.

Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor

1994 ◽  
Vol 266 (6) ◽  
pp. L593-L611 ◽  
Author(s):  
M. D. Evans ◽  
W. A. Pryor
Keyword(s):  
Cigarette Smoke ◽  
Proteinase Inhibitor ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Tissue Destruction ◽  
Phagocytic Cells ◽  
Lung Fluid

The proteinase-antiproteinase theory for the pathogenesis of emphysema proposes that the connective tissue destruction associated with emphysema arises from excessive proteinase activity in the lower respiratory tract. For this reason, the relative activities of neutrophil elastase and alpha 1-proteinase inhibitor (alpha 1-PI) are considered important. Most emphysema is observed in smokers; therefore, alpha 1-PI has been studied as a target for smoke-induced damage. Damage to alpha 1-PI in lung fluid could occur by several mechanisms involving species delivered to the lung by cigarette smoke and/or stimulated inflammatory cells. Oxidative damage to alpha 1-PI has received particular attention, since both cigarette smoke and inflammatory cells are rich sources of oxidants. In this article we review almost two decades of research on mechanistic studies of damage to alpha 1-PI by cigarette smoke and phagocytic cells in vitro, studies emphasizing the importance of elastinolytic activity in the pathogenesis of emphysema in vivo and studies of human lung lavage fluid to detect defects in alpha 1-PI at the molecular and functional levels.

scholarly journals Human neutrophil lipocalin (HNL) and myeloperoxidase (MPO). Studies of lung lavage fluid and lung tissue

2000 ◽  
Vol 94 (6) ◽  
pp. 564-568 ◽  
Author(s):  
B. SCHMEKEL ◽  
L. SEVEUS ◽  
S.Y. XU ◽  
P. VENGE
Keyword(s):  
Lung Tissue ◽  
Human Neutrophil ◽  
Lavage Fluid ◽  
Lung Lavage

scholarly journals Effects of CX3CL1 inhibition on murine bleomycin-induced interstitial pneumonia

2020 ◽  
Vol 18 ◽  
pp. 205873922095990
Author(s):  
Soichi Yamada ◽  
Shion Miyoshi ◽  
Junko Nishio ◽  
Satoshi Mizutani ◽  
Zento Yamada ◽  
...  
Keyword(s):  
Interstitial Pneumonia ◽  
T Cell Activation ◽  
Lung Tissue ◽  
Cell Activation ◽  
Immunohistochemical Analysis ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Novel Therapy ◽  
Tissue Sections

Background: Treatment for interstitial pneumonia (IP) associated with collagen diseases has not been established. There is a need to elucidate the pathogenesis of IP and develop a novel therapy. We aimed to clarify the role of chemokine (C-X3-C motif) ligand 1 (CX3CL1, also known as fractalkine) in IP. Methods: Bleomycin (BLM) was intratracheally administered to C57BL/6 mice to induce IP. For treatment with control Ab or anti-CX3CL1 mAb, the mice were administered either Ab three times per week for 2 weeks from the day of BLM administration until euthanasia. Expressions of CX3CL1 and its unique receptor CX3CR1 in the lung tissue were examined by immunohistochemical analysis. Cellular infiltration and lung fibrosis were evaluated based on hematoxylin-eosin-staining and Sirius red staining of the lung tissue sections, respectively. Bronchoalveolar lavage fluid (BALF) cells were analyzed by flow cytometry. Results: CX3CL1 and CX3CR1 were strongly expressed in the lung tissue from mice with BLM-induced IP (BLM-IP). Treatment with anti-CX3CL1 mAb did not significantly alter inflammatory cell infiltration or fibrosis in the lung tissue. However, the number of M1-like macrophages in BALF was decreased and surface CD3 expression on T cells was increased by anti-CX3CL1 mAb treatment. Conclusions: Inhibition of CX3CL1 decreased inflammatory cells and may attenuate T cell activation in BALF. CX3CL1 inhibitor may have the potential to suppress the infiltration and activation of immune cells in IP.

Differential NF-κB activation after intratracheal endotoxin

1999 ◽  
Vol 277 (4) ◽  
pp. L823-L830 ◽  
Author(s):  
Timothy S. Blackwell ◽  
Lisa H. Lancaster ◽  
Thomas R. Blackwell ◽  
Annapurna Venkatakrishnan ◽  
John W. Christman
Keyword(s):  
Lung Tissue ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Binding Activity ◽  
Cytokine Gene Expression ◽  
Dna Binding Activity ◽  
Factor Α ◽  
The Relationship ◽  
Second Peak ◽  
Necrosis Factor

We examined the relationship between nuclear factor (NF)-κB DNA binding activity, cytokine gene expression, and neutrophilic alveolitis in rats after intratracheal (IT) instillation of endotoxin [lipopolysaccharide (LPS)]. NF-κB activation in lung tissue mirrored neutrophilic alveolitis after IT LPS instillation, with NF-κB activation and neutrophilic influx beginning 2 h after IT LPS doses of 0.01 mg/kg or greater. In lung lavage fluid cells, however, transient NF-κB activation was present in alveolar macrophages by 15 min after IT LPS instillation, followed by a second peak of NF-κB activation corresponding to the onset on neutrophilic alveolitis. For cytokines thought to be NF-κB dependent, two different patterns of mRNA expression were found. Interleukin (IL)-1α, IL-1β, and tumor necrosis factor-α showed increased mRNA by 30 min after IT LPS instillation, but IL-6- and cytokine-induced neutrophil chemoattractant mRNAs were not substantially increased until 2 h after IT LPS instillation. Therefore, IT LPS causes differential NF-κB activation in air space cells and lung tissue, which likely determines production of key cytokines and directs the evolution of neutrophilic alveolitis.

scholarly journals Cavidine protects against asthma in neonatal asthmatic mice model by attenuating PI3Ks/NF-κB signaling pathway

2021 ◽  
Vol 18 (3) ◽  
pp. 513-518
Author(s):  
Qin Hao ◽  
Juan Shen ◽  
Lin Zhao
Keyword(s):  
Signaling Pathway ◽  
Treatment Protocol ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Mice Model ◽  
Altered Expression ◽  
Neonatal Mice ◽  
Cytokine Levels ◽  
Asthmatic Group

Purpose: To evaluate the protective effect of cavidine against asthma in neonatal mice. Methods: Neonatal mice were treated with cavidine at doses of 5 and 10 mg/kg, po, 2 h prior to asthma induction with ovalbumin (OVA) on the 1st and 14th days of the treatment protocol. The anti-asthma activity of cavidine was evaluated by determining the number of inflammatory cells and cytokine levels in broncho-alveolar lavage fluid (BALF) and OVA-specific IgE and TGF-β 1 in the serum of OVAsensitized mice. The levels of NF-ƙB and PI3K protein expression were determined in the lung tissues of OVA-sensitized mice. Results: Cavidine attenuated the number of inflammatory cells and cytokines in BALF of OVAsensitized mice. The levels of OVA-specific IgE and TGF-β 1 decreased significantly in cavidine-treated groups, when compared to asthmatic group of mice, while NF-ƙB was significantly downregulated (p < 0.01). The altered expression of PI3K signaling protein was attenuated in the lung tissues of cavidinetreated mice sensitized with OVA. Conclusion: These results reveal that the anti-asthma effect of cavidine in OVA-induced asthmatic neonatal mice occurs via reduction of inflammation and immune responsive cells linked to PI3Ks/ NF-κB signaling pathway in lung tissues. These findings suggest that cavidine may be clinically suitable for the management of asthma.

scholarly journals Impact of Surfactant Protein D, Interleukin-5, and Eosinophilia on Cryptococcosis

2013 ◽  
Vol 82 (2) ◽  
pp. 683-693 ◽  
Author(s):  
Stephanie M. Holmer ◽  
Kathy S. Evans ◽  
Yohannes G. Asfaw ◽  
Divey Saini ◽  
Wiley A. Schell ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Infections ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Lung Lavage ◽  
Eosinophil Infiltration ◽  
Surfactant Protein D ◽  
Content Type ◽  
Interleukin 5

ABSTRACTCryptococcus neoformansis an opportunistic fungal pathogen that initiates infection following inhalation. As a result, the pulmonary immune response provides a first line of defense againstC. neoformans. Surfactant protein D (SP-D) is an important regulator of pulmonary immune responses and is typically host protective against bacterial and viral respiratory infections. However, SP-D is not protective againstC. neoformans. This is evidenced by previous work from our laboratory demonstrating that SP-D-deficient mice infected withC. neoformanshave a lower fungal burden and live longer than wild-type (WT) control animals. We hypothesized that SP-D alters susceptibility toC. neoformansby dysregulating the innate pulmonary immune response following infection. Thus, inflammatory cells and cytokines were compared in the bronchoalveolar lavage fluid from WT and SP-D−/−mice afterC. neoformansinfection. Postinfection, mice lacking SP-D have reduced eosinophil infiltration and interleukin-5 (IL-5) in lung lavage fluid. To further explore the interplay of SP-D, eosinophils, and IL-5, mice expressing altered levels of eosinophils and/or IL-5 were infected withC. neoformansto assess the role of these innate immune mediators. IL-5-overexpressing mice have increased pulmonary eosinophilia and are more susceptible toC. neoformansinfection than WT mice. Furthermore, susceptibility of SP-D−/−mice toC. neoformansinfection could be restored to the level of WT mice by increasing IL-5 and eosinophils by crossing the IL-5-overexpressing mice with SP-D−/−mice. Together, these studies support the conclusion that SP-D increases susceptibility toC. neoformansinfection by promotingC. neoformans-driven pulmonary IL-5 and eosinophil infiltration.

Role of peptidoleukotrienes in hypoxic pulmonary vasoconstriction in rats

1990 ◽  
Vol 259 (3) ◽  
pp. H751-H758 ◽  
Author(s):  
T. J. McDonnell ◽  
J. Y. Westcott ◽  
J. Czartolomna ◽  
N. F. Voelkel
Keyword(s):  
Lung Tissue ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Physiological Salt Solution ◽  
Slight Reduction ◽  
Lipoxygenase Inhibitor ◽  
Pulmonary Vasoconstriction ◽  
Eicosanoid Production

The role of leukotrienes in the mechanism of hypoxic pulmonary vasoconstriction (HPV) is controversial. To determine whether leukotriene C4 (LTC4) was produced during HPV, LTC4 levels were measured in individual samples of lung tissue, lung bronchoalveolar lavage fluid (BALF), and blood perfusate in isolated perfused lungs ventilated with normoxic or hypoxic gas mixtures. HPV was not associated with increased LTC4 in lung tissue or increased LTE4 in blood perfusate. Consistent with previous studies demonstrating elevated levels of LTC4 in pooled BALF fluid from hypoxic lungs, individual lung BALF samples demonstrated an elevation of LTC4 during hypoxia. However, the process of lung lavage alone stimulated eicosanoid production, with LTC4, 6-ketoprostaglandin F1 alpha, and thromboxane B2 levels being higher in lavaged compared to non-lavaged lungs. In lungs to which the lipoxygenase inhibitor AA 861 was added to the perfusate, a reduction in the lung tissue LTC4 levels was observed without any or only a slight reduction in HPV. To evaluate the physiological effects of LTC4 in the airways, exogenous LTC4 (1-1,000 ng) was added to the airways of both blood- and physiological salt solution-perfused lungs without any effect on the pulmonary artery pressure or a response to hypoxia. These results do not support the hypothesis that leukotrienes mediate HPV in the rat.

scholarly journals Lung Protection Strategies during Cardiopulmonary Bypass Affect the Composition of Bronchoalveolar Fluid and Lung Tissue in Cardiac Surgery Patients

Metabolites ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 54 ◽  
Author(s):  
Raluca Maltesen ◽  
Katrine Buggeskov ◽  
Claus Andersen ◽  
Ronni Plovsing ◽  
Reinhard Wimmer ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Lung Tissue ◽  
Ischemia Reperfusion ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Acid Oxidation ◽  
Pulmonary Perfusion ◽  
Standard Regimen ◽  
Lung Protection ◽  
Cell Counts

Pulmonary dysfunction is among the most frequent complications to cardiac surgeries. Exposure of blood to the cardiopulmonary bypass (CPB) circuit with subsequent lung ischemia-reperfusion leads to the production of inflammatory mediators and increases in microvascular permeability. The study aimed to elucidate histological, cellular, and metabolite changes following two lung protective regimens during CPB with Histidine-Tryptophan-Ketoglutarate (HTK) enriched or warm oxygenated blood pulmonary perfusion compared to standard regimen with no pulmonary perfusion. A total of 90 patients undergoing CPB were randomized to receiving HTK, oxygenated blood or standard regimen. Of these, bronchoalveolar lavage fluid (BALF) and lung tissue biopsies were obtained before and after CPB from 47 and 25 patients, respectively. Histopathological scores, BALF cell counts and metabolite screening were assessed. Multivariate and univariate analyses were performed. Profound histological, cellular, and metabolic changes were identified in all patients after CPB. Histological and cellular changes were similar in the three groups; however, some metabolite profiles were different in the HTK patients. While all patients presented an increase in inflammatory cells, metabolic acidosis, protease activity and oxidative stress, HTK patients seemed to be protected against severe acidosis, excessive fatty acid oxidation, and inflammation during ischemia-reperfusion. Additional studies are needed to confirm these findings.

Influence of fasting on the lung

1977 ◽  
Vol 42 (1) ◽  
pp. 88-92 ◽  
Author(s):  
D. B. Gail ◽  
G. D. Massaro ◽  
D. Massaro
Keyword(s):  
Lung Tissue ◽  
Surface Film ◽  
Lavage Fluid ◽  
Volume Density ◽  
Lung Lavage ◽  
Lamellar Bodies ◽  
Monomolecular Film ◽  
Residual Capacity ◽  
Alveolar Stability ◽  
Fasted Rats

We examined the following in fed rats and in rats fasted for 72 h: 1) the dipalmitoyl lecithin (DPL) content of lung lavage fluid and of the remaining lung tissue, 2) descending air and saline pressure-volume curves of excised lungs, and 3) the volume density of granular pneumocyte lamellar bodies. Lung tissue DPL was decreased by 27% and lavage DPL was decreased by 40% in lungs of fasted rats. The decreased lung DPL content was associated with a 20% decrease in the volume density of lamellar bodies of granular pneumocytes. In spite of the decrease in lavage DPL content, air pressure-volume curves of excised lungs were the same as curves of lungs of fed rats. Saline pressure-volume curves of excised lungs were also the same in fed and fasted rats. The amount of lavage DPL obtained from both fed (1.1 +/- 0.1 mg, n=6) and fasted (0.7 +/- 0.1 mg, n=7) rats exceeded the theoretical minimum amount of DPL (0.5 mg) required for a monomolecular film to cover the alveolar surface of the rat at functional residual capacity. If we assume that lavage DPL represents mainly DPL lining the alveolus (surface film and hypophase) the data suggest that there is an alveolar reserve of DPL above that amount needed to maintain normal alveolar stability.

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