Browsing by Subject "Emphysema"

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    A comparative study of extracellular matrix remodeling in two murine models of emphysema
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2013) Lopes, F.D.T.Q.S.; Toledo, A.C.; Olivo, C.R.; Prado, C.M.; Leick, E.A.; Medeiros, M.C.; Santos, A.B.G.; Garippo, A.; Martins, M.A.; Mauad, T.
    A single instillation of porcine pancreatic elastase (PPE) results in significant airspace enlargement on the 28th day after instillation, whereas cigarette smoke (CS) exposure requires 6 months to produce mild emphysema in rodents. Considering that there are differences in the pathogenesis of parenchymal destruction in these different experimental models, it is likely that there may be different patterns of extracellular matrix (ECM) remodeling. To evaluate ECM remodeling, C57BL/6 mice were submitted to either a nasal drop of PPE (PPE 28 Days) or exposed for 6 months to cigarette smoke (CS 6 months). Control groups received either an intranasal instillation of saline solution (Saline 28 Days) or remained without any smoke inhalation for six months (Control 6 months). We measured the mean linear intercept and the volume proportion of collagen type I, collagen type III, elastin and fibrillin. We used emission-scanning confocal microscopy to verify the fiber distribution. Both models induced increased mean linear intercept in relation to the respective controls, being larger in the elastase model in relation to the CS model. In the CS model, emphysema was associated with an increase in the volume proportion of fibrillin, whereas in the PPE model there was an increase in the parenchymal elastin content. In both models, there was an increase in collagen type III, which was higher in the CS-exposed mice. We concluded that ECM remodeling is different in the two most used experimental models of emphysema.
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    Morphogenesis of rat experimental pulmonary emphysema induced by intratracheally administered papain: changes in elastic fibres
    (Murcia : F. Hernández, 2006) Sánchez-Gascón, F.; Girona, J.C.; Bernal-Mañas, C.M.; Morales, E.; Canteras, M.; Beltrán Frutos, Ester; Pastor García, Luis Miguel
    The ultrastructural changes of elastic fibres in emphysematous lungs have been studied in men, but few works exist on this topic in experimental emphysematous animals. In this paper, the morphogenesis of emphysema and alterations of the elastic fibres produced by the instillation of papain are described by light and electron microscopy. Wistar rats were instilled through the trachea with papain at a rate of 3 mg/100 g animal weight. The animals were sacrificed 12 h, 3 days, 10 days and 60 days after enzyme instillation. The "Mean Linear Intercept" (MLI), the "Number of fenestrations/respiratory units" (NF) the “Number of macrophages per mm of alveolar wall” (NM) and the "Number of respiratory unit/mm2” (RU), both in the control and experimental groups were studied. Two months after treatment, the experimental group showed a strong increase in the MLI (p<0.001) and NF (p<0.001), and a diminished number of RU (p<0.05) compared with the control group. Partial correlation analysis showed a positive correlation only between MLI and NF. Twelve hours after papain instillation an inflammatory response was observed, the elastic fibres were ruptured, while the microfibrilar component remained. New formations of eulanin elastic fibres were observed three days post papain instillation. After ten days the interalveolar oedema had disappeared and the elastic fibres were of normal morphology although irregular groups of strips of elastic fibres were evident. A mixed pattern of panlobular, centrilobular and normal lung zones were observed. Two months after papain instillation abundant accumulations of elastic fibres of irregular outline were observed associated to collagen fibres. In conclusion, the morphometric parameters studied showed a significant progression of the emphysema. The strong correlation between NF and MLI suggested that papain-induced emphysema is principally caused by breaches of the alveolar walls. The results seem to point to a very abnormal remodelling process associated with elastic fibre regeneration, although there were no signs of destruction of these new fibres formed in emphysematous rat lung induced by papain.
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    The contribution of type II pneumocytes and alveolar macrophages to fibroplasia processes in the course of enzymatic lung injury
    (Murcia : F. Hernández, 1997) Sulkowska, M.; Sulkowski, S.
    The aim of the paper was to evaluate mutual relations in the system of alveolar macrophage (AM) - type 11 pneumocyte (PII) - interstitium of alveolar septa, in the course of experimental lung emphysema in rats subjected to BCG vaccine effect. Administration of BCG vaccine resulted in the cumulation of AM within pulmonary alveoli. These cells exhibited morphological features of increased activity. Intratracheal papain injection induced intralobular emphysema changes, partly generalized, in the animal lungs. The emphysematous changes, with domination of interalveolar septum atrophy, were accompanied by foca1 accumulation of collagen and elastin. Fibroplasia processes were strongly pronounced in BCG- and papain-treated animals. The areas of connective tissue fibres cumulation revealed indistinctness of the boundary line between PII and the interstitium in some places. Anchorage of collagen fibres and microfibrillary structures were observed in the cytoplasm of PII. The morphological examinations of AM - fibroblasts co-cultures as well as the evaluation of the uptake of 3 ~ - thymidine did not show any significant differences between respective co-cultures of fibroblasts and AM isolated both from the lungs of control and experimental animals (treated with BCG or papain, and BCG+papain). However, a significant growth was noted in 3 ~ - thymidine uptake between fibroblast cultures realized with or without cells isolated from the lungs. The results obtained suggest the possibility of active participation of PII and AM in fibroplasia processes in the course of lung rebuilding after papain administration and in pathological states of the pulmonary tissue, particularly when they are accompanied by increased activity of alveolar macrophages. They also support the inflammatory-repair hypothesis in the development of emphysematous changes.
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    The tick-derived rBmTI-A protease inhibitor attenuates the histological and functional changes induced by cigarette smoke exposure
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Lourenço, Juliana D.; Ito, Juliana T.; Cervilha, Daniela A.B.; Sales, Davi S.; Riani, Alyne; Suehiro, Camila L.; Genaro, Isabella S.; Duran, Adriana; Puzer, Luciano; Martins, Milton A.; Sasaki, Sérgio D.; Lopes, Fernanda D.T.Q.S.
    Introduction. Smoking is the main risk factor for chronic obstructive pulmonary disease development and cigarette smoke (CS) exposure is considered an important approach to reproduce in rodents this human disease. We have previously shown that in an elastase-induced model of emphysema, the administration of a protease inhibitor (rBmTI-A) prevented and attenuated tissue destruction in mice. Thus, in this study we aimed to verify the effects of rBmTI-A administration on the physiopathological mechanisms of CS-induced emphysema. Methods. Mice (C57BL/6) were exposed to CS or room air for 12 weeks. In this period, 3 nasal instillations of rBmTI-A inhibitor or its vehicle were performed. After euthanasia, respiratory mechanics were evaluated and lungs removed for analysis of mean linear intercept, volume proportion of collagen and elastic fibers, density of polymorphonuclear cells, macrophages, and density of positive cells for MMP-12, MMP-9, TIMP-1 and gp91phox. Results. The rBmTI-A administration improved tissue elastance, decreased alveolar enlargement and collagen fibers accumulation to control levels and attenuated elastic fibers accumulation in animals exposed to CS. There was an increase of MMP12, MMP-9 and macrophages in CS groups and the rBmTIA only decreased the number of MMP-12 positive cells. Also, we demonstrated an increase in gp91phox in CS treated group and in TIMP-1 levels in both rBmTI-A treated groups. Conclusion. In summary, the rBmTI-A administration attenuated emphysema development by an increase of gp91phox and TIMP-1, accompanied by a decrease in MMP-12 levels.
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    Tobacco smoke and age as risk factors in emphysema. Morphometrical study on the rat
    (Murcia : F. Hernández, 1996) Escolar Castellón, J.de D.; Martínez, M.N.; Escolar, M.A.; Arranz, M.; Gallego, B.; Roche Roche, P.A.
    During ageing, a progressive deterioration in the pulmonary function, which can be accelerated by exposure to tobacco smoke, takes place. The hypothesis that the initial age of exposure to tobacco smoke is a factor of utmost importance in the development of ernphysema is proposed. Eighty-six rats, aged nineteen months at the time of sacrifice, were used and were ordered into three groups: the first group consisted of unrnanipulated animals; the second, of animals which had been exposed to tobacco smoke from the age of twelve months to the age of nineteen months; and the third, of animals which had been exposed to tobacco smoke from the age of nine months to the age of twelve months. The lungs of the animals were histologically processed for light microscopy and were studied morphometrically by computer. Eleven quantitative variables were quantified and ordered into three groups: variables related with alveolar enlargement; variables related with tissue loss; and variables related with the elastic fibre. The number of animals in which alveolar enlargement and tissue destruction concurred was counted, thus enabling the attributable and relative risks of developing emphysema to be calculated in the two groups of rnanipulated anirnals. From the results it is clear that, when compared with the unmanipulated group, the two groups which had been exposed to tobacco smoke displayed an increase in the variables which quantified alveolar enlargernent and a decrease in those which measured tissue loss; these results were more significant in the third group (p<0.001) than in the second ( ~ ~ 0 . 0 5s)i;g nificant differences were also found between these two groups of animals. The relative risk and attributable risks of developing emphyserna were 2.41 and 28.15 respectively in the second group and 3.48 and 34.48 in the third group. Our results lead us to propose that the risk of developing emphysema exists in inverse proportion to the initial age of exposure to tobacco smoke.