Different strains of mice present distinct lung tissue mechanics and extracellular matrix composition in a model of chronic allergic asthma

2009 ◽  
Vol 165 (2-3) ◽  
pp. 202-207 ◽  
Author(s):  
Mariana A. Antunes ◽  
Soraia C. Abreu ◽  
Nilsa R. Damaceno-Rodrigues ◽  
Edwin R. Parra ◽  
Vera L. Capelozzi ◽  
...  
2006 ◽  
Vol 152 (2) ◽  
pp. 186-196 ◽  
Author(s):  
Debora S. Faffe ◽  
Elizabeth S. D’Alessandro ◽  
Debora G. Xisto ◽  
Mariana A. Antunes ◽  
Pablo V. Romero ◽  
...  

2001 ◽  
Vol 90 (4) ◽  
pp. 1400-1406 ◽  
Author(s):  
Débora S. Faffe ◽  
Gabriela H. Silva ◽  
Pedro M. P. Kurtz ◽  
Elnara M. Negri ◽  
Vera L. Capelozzi ◽  
...  

The dynamic mechanical properties of lung tissue and its contents of collagen and elastic fibers were studied in strips prepared from mice instilled intratracheally with saline (C) or silica [15 (S15) and 30 days (S30) after instillation]. Resistance, elastance, and hysteresivity were studied during oscillations at different frequencies on S15 and S30. Elastance increased from C to silica groups but was similar between S15 and S30. Resistance was augmented from C to S15 and S30 and was greater in S30 than in S15 at higher frequencies. Hysteresivity was higher in S30 than in C and S15. Silica groups presented a greater amount of collagen than did C. Elastic fiber content increased progressively along time. This increment was related to the higher amount of oxytalan fibers at 15 and 30 days, whereas elaunin and fully developed elastic fibers were augmented only at 30 days. Silicosis led not only to pulmonary fibrosis but also to fibroelastosis, thus assigning a major role to the elastic system in the silicotic lung.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Pengfei Xu ◽  
Fabian Gärtner ◽  
Adrian Gihring ◽  
Congxing Liu ◽  
Timo Burster ◽  
...  

Abstract Background Previously, it has been shown that obesity is a risk factor for recovery, regeneration, and tissue repair after blunt trauma and can affect the rate of muscle recovery and collagen deposition after trauma. To date, lung tissue regeneration and extracellular matrix regulation in obese mice after injury has not been investigated in detail yet. Methods This study uses an established blunt thorax trauma model to analyze morphological changes and alterations on gene and protein level in lean or obese (diet-induced obesity for 16 ± 1 week) male C57BL/6 J mice at various time-points after trauma induction (1 h, 6 h, 24 h, 72 h and 192 h). Results Morphological analysis after injury showed lung parenchyma damage at early time-points in both lean and obese mice. At later time-points a better regenerative capacity of lean mice was observed, since obese animals still exhibited alveoli collapse, wall thickness as well as remaining filled alveoli structures. Although lean mice showed significantly increased collagen and fibronectin gene levels, analysis of collagen deposition showed no difference based on colorimetric quantification of collagen and visual assessment of Sirius red staining. When investigating the organization of the ECM on gene level, a decreased response of obese mice after trauma regarding extracellular matrix composition and organization was detectable. Differences in the lung tissue between the diets regarding early responding MMPs (MMP8/9) and late responding MMPs (MMP2) could be observed on gene and protein level. Obese mice show differences in regulation of extracellular matrix components compared to normal weight mice, which results in a decreased total MMP activity in obese animals during the whole regeneration phase. Starting at 6 h post traumatic injury, lean mice show a 50% increase in total MMP activity compared to control animals, while MMP activity in obese mice drops to 50%. Conclusions In conclusion, abnormal regulation of the levels of extracellular matrix genes in the lung may contribute to an aberrant regeneration after trauma induction with a delay of repair and pathological changes of the lung tissue in obese mice.


2008 ◽  
Vol 294 (6) ◽  
pp. L1197-L1205 ◽  
Author(s):  
Patrícia Angeli ◽  
Carla M. Prado ◽  
Débora G. Xisto ◽  
Pedro L. Silva ◽  
Caroline P. Pássaro ◽  
...  

The importance of lung tissue in asthma pathophysiology has been recently recognized. Although nitric oxide mediates smooth muscle tonus control in airways, its effects on lung tissue responsiveness have not been investigated previously. We hypothesized that chronic nitric oxide synthase (NOS) inhibition by Nω-nitro-l-arginine methyl ester (l-NAME) may modulate lung tissue mechanics and eosinophil and extracellular matrix remodeling in guinea pigs with chronic pulmonary inflammation. Animals were submitted to seven saline or ovalbumin exposures with increasing doses (1∼5 mg/ml for 4 wk) and treated or not with l-NAME in drinking water. After the seventh inhalation (72 h), animals were anesthetized and exsanguinated, and oscillatory mechanics of lung tissue strips were performed in baseline condition and after ovalbumin challenge (0.1%). Using morphometry, we assessed the density of eosinophils, neuronal NOS (nNOS)- and inducible NOS (iNOS)-positive distal lung cells, smooth muscle cells, as well as collagen and elastic fibers in lung tissue. Ovalbumin-exposed animals had an increase in baseline and maximal tissue resistance and elastance, eosinophil density, nNOS- and iNOS-positive cells, the amount of collagen and elastic fibers, and isoprostane-8-PGF2α expression in the alveolar septa compared with controls ( P < 0.05). l-NAME treatment in ovalbumin-exposed animals attenuated lung tissue mechanical responses ( P < 0.01), nNOS- and iNOS-positive cells, elastic fiber content ( P < 0.001), and isoprostane-8-PGF2α in the alveolar septa ( P < 0.001). However, this treatment did not affect the total number of eosinophils and collagen deposition. These data suggest that NO contributes to distal lung parenchyma constriction and to elastic fiber deposition in this model. One possibility may be related to the effects of NO activating the oxidative stress pathway.


2001 ◽  
Vol 164 (6) ◽  
pp. 1067-1071 ◽  
Author(s):  
PATRICIA R. M. ROCCO ◽  
ELNARA M. NEGRI ◽  
PEDRO M. KURTZ ◽  
FERNANDA P. VASCONCELLOS ◽  
GABRIELA H. SILVA ◽  
...  

2001 ◽  
Vol 281 (5) ◽  
pp. L1078-L1087 ◽  
Author(s):  
Rehab Al-Jamal ◽  
Mara S. Ludwig

Excessive mechanical ventilation results in changes in lung tissue mechanics. We hypothesized that changes in tissue properties might be related to changes in the extracellular matrix component proteoglycans (PGs). The effect of different ventilation regimens on lung tissue mechanics and PGs was examined in an in vivo rat model. Animals were anesthetized, tracheostomized, and ventilated at a tidal volume of 8 (Vt 8), 20, or 30 (Vt 30) ml/kg, positive end-expiratory pressure of 0 (PEEP0) or 1.5 (PEEP1.5) cmH2O, and frequency of 1.5 Hz for 2 h. The constant-phase model was used to derive airway resistance, tissue elastance, and tissue damping. After physiological measurements, one lung was frozen for immunohistochemistry and the other was reserved for PG extraction and Western blotting. After 2 h of mechanical ventilation, tissue elastance and damping were significantly increased in rats ventilated at Vt 30PEEP0 compared with control rats (ventilated at Vt 8PEEP1.5). Versican, basement membrane heparan sulfate PG, and biglycan were all increased in rat lungs ventilated at Vt 30PEEP0 compared with control rats. At Vt 30PEEP0, heparan sulfate PG and versican staining became prominent in the alveolar wall and airspace; biglycan was mostly localized in the airway wall. These data demonstrate that alterations in lung tissue mechanics with excessive mechanical ventilation are accompanied by changes in all classes of extracellular matrix PG.


2016 ◽  
Vol 310 (4) ◽  
pp. L311-L327 ◽  
Author(s):  
Aline Vuckovic ◽  
Susanne Herber-Jonat ◽  
Andreas W. Flemmer ◽  
Ina M. Ruehl ◽  
Carmela Votino ◽  
...  

Survivors of severe congenital diaphragmatic hernia (CDH) present significant respiratory morbidity despite lung growth induced by fetal tracheal occlusion (TO). We hypothesized that the underlying mechanisms would involve changes in lung extracellular matrix and dysregulated transforming growth factor (TGF)-β pathway, a key player in lung development and repair. Pulmonary expression of TGF-β signaling components, downstream effectors, and extracellular matrix targets were evaluated in CDH neonates who died between birth and the first few weeks of life after prenatal conservative management or TO, and in rabbit pups that were prenatally randomized for surgical CDH and TO vs. sham operation. Before tissue harvesting, lung tissue mechanics in rabbits was measured using the constant-phase model during the first 30 min of life. Human CDH and control fetal lungs were also collected from midterm onwards. Human and experimental CDH did not affect TGF-β/Smad2/3 expression and activity. In human and rabbit CDH lungs, TO upregulated TGF-β transcripts. Analysis of downstream pathways indicated increased Rho-associated kinases to the detriment of Smad2/3 activation. After TO, subtle accumulation of collagen and α-smooth muscle actin within alveolar walls was detected in rabbit pups and human CDH lungs with short-term mechanical ventilation. Despite TO-induced lung growth, mediocre lung tissue mechanics in the rabbit model was associated with increased transcription of extracellular matrix components. These results suggest that prenatal TO increases TGF-β/Rho kinase pathway, myofibroblast differentiation, and matrix deposition in neonatal rabbit and human CDH lungs. Whether this might influence postnatal development of sustainably ventilated lungs remains to be determined.


2008 ◽  
Vol 104 (6) ◽  
pp. 1778-1785 ◽  
Author(s):  
Adriane S. Nakashima ◽  
Carla M. Prado ◽  
Tatiana Lanças ◽  
Viviane C. Ruiz ◽  
David I. Kasahara ◽  
...  

Recent studies emphasize the presence of alveolar tissue inflammation in asthma. Immunotherapy has been considered a possible therapeutic strategy for asthma, and its effect on lung tissue had not been previously investigated. Measurements of lung tissue resistance and elastance were obtained before and after both ovalbumin and acetylcholine challenges. Using morphometry, we assessed eosinophil and smooth muscle cell density, as well as collagen and elastic fiber content, in lung tissue from guinea pigs with chronic pulmonary allergic inflammation. Animals received seven inhalations of ovalbumin (1–5 mg/ml; OVA group) or saline (SAL group) during 4 wk. Oral tolerance (OT) was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st inhalation (OT1 group) or after the 4th (OT2 group). The ovalbumin-exposed animals presented an increase in baseline and in postchallenge resistance and elastance related to baseline, eosinophil density, and collagen and elastic fiber content in lung tissue compared with controls. Baseline and post-ovalbumin and acetylcholine elastance and resistance, eosinophil density, and collagen and elastic fiber content were attenuated in OT1 and OT2 groups compared with the OVA group. Our results show that inducing oral tolerance attenuates lung tissue mechanics, as well as eosinophilic inflammation and extracellular matrix remodeling induced by chronic inflammation.


Sign in / Sign up

Export Citation Format

Share Document