Trichloroethylene induces pulmonary fibrosis in mice

1994 ◽  
Vol 72 (3) ◽  
pp. 205-210 ◽  
Author(s):  
P. G. Forkert ◽  
L. Forkert

Trichloroethylene elicits acute pulmonary cytotoxicity in mice, which involves Clara cells of bronchioles. In this study, we have examined the effects of an acute dose of trichloroethylene in lungs of mice over 3 months. Pulmonary fibrosis was first detected at 15 days and was progressive with time elapsed after trichloroethylene exposure. Diffuse interstitial fibrosis was observed in the alveolar zone, resulting in thickening of alveolar septa and distortion of lung structure. The fibrosis was most pronounced at 90 days after treatment, resulting in deposition of connective tissue in the alveolar septa. Levels of total lung hydroxyproline were not significantly different in control and treated mice at 30 and 60 days after trichloroethylene treatment, but were significantly increased at 90 days. Proline content remained unchanged during the course of this study. The increase in collagen deposition at 90 days coincided with a signficant increase in lung elastic recoil. Our results show that a single acute dose of trichloroethylene causes structural and functional abnormalities that are progressive for at least 3 months.Key words: trichloroethylene, lung, interstitial fibrosis.

1996 ◽  
Vol 81 (6) ◽  
pp. 2468-2480 ◽  
Author(s):  
E. K. Verbeken ◽  
M. Cauberghs ◽  
K. P. Van De Woestijne

Verbeken, E. K., M. Cauberghs, and K. P. Van de Woestijne.Membranous bronchioles and connective tissue network of normal and emphysematous lungs. J. Appl. Physiol.81(6): 2468–2480, 1996.—Three-dimensional reconstructions of the septal system of normal human lungs revealed that airways course within the interlobular septa, i.e., between the two blades formed by the peripheral boundaries of adjacent lobuli of whatever order, and enter the supplied pulmonary unit at its side. This is not in keeping with the classic view of a peripheral airway in the center of a lung unit and submitted to radial traction by attached alveolar septa. The basic design of the lung fibrous scaffold appears to be in conformity with the laws of fractal geometry. Similar reconstructions in centrilobular emphysema disclosed tortuosities of both intra-acinar and interlobular septa, with consequent distortions of the corresponding intraseptal bronchioles and collapse of lung units of different sizes. It is suggested that in centrilobular emphysema competition for space, besides intrinsic airways narrowing because of inflammation and loss of elastic recoil, is a cause of flow limitation.


1994 ◽  
Vol 77 (3) ◽  
pp. 1060-1066 ◽  
Author(s):  
R. R. Mercer ◽  
M. L. Russell ◽  
J. D. Crapo

Because the retractive forces due to surface tension decrease with increasing radius of curvature, there should be a greater contribution to lung recoil attributable to the stress-bearing role of elastic elements in the lung parenchyma of species with larger alveoli. To examine alterations in lung structure that may relate to this stress-bearing role, the lungs of mice, hamsters, rats, rabbits, rhesus monkeys, baboons, and humans were preserved by vascular perfusion of fixative. The number of alveoli per lung, alveolar radius of curvature, surface area, and volume were measured by serial section reconstruction. Electron-microscopic determinations were made of the volume fraction and thickness of the epithelium, interstitium, and endothelium and of the connective tissue fibers of the alveolar septa and the portions of alveolar septa that form the alveolar ducts. The thickness of the alveolar septal interstitium increased linearly with the increase in radius of curvature of alveoli. The increase in interstitial thickness in lungs with larger alveoli was paralleled by large increases in the volume of collagen and elastin fibers present in this space. Comparable changes in the thickness of connective tissue fibers in alveolar duct walls were also found. This study demonstrates species-related changes in the structure of alveolar septa and in lung collagen and elastin fibers that are consistent with connective tissue fibers having a greater stress-bearing role in both the alveolar septa and alveolar ducts of species with larger alveoli.


2020 ◽  
Vol 19 (5) ◽  
pp. 971-976
Author(s):  
Xiangwei Qi ◽  
Yamei Ou ◽  
Ying Xie ◽  
Kangrong Cai ◽  
Hualin Gan ◽  
...  

Purpose: To determine the functional effect of chrysophanol (CH) on bleomycin (BLM)-induced pulmonary fibrosis (PF) and reveal its mechanism of action.Methods: A mouse model of PF was established by intratracheal instillation of BLM (5 mg/kg), prior to CH administration. Masson’s trichrome staining was used to analyze interstitial fibrosis and collagen deposition. Hydroxyproline (HYP) content was measured, and lung fibroblast viability determined by MTT assay. Bronchoalveolar lavage fluid (BALF) was collected, and levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and interferon-γ (IFN-γ) were evaluated using enzyme-linked immunosorbent assays (ELISA). Expression of cell signaling, adhesion, and apoptotic proteins were determined by western blotting.Results: Administration of CH reduced collagen deposition and HYP content, downregulated α-smooth muscle actin, upregulated E-cadherin, and decreased the levels of TNF-α, IL-1β, IL-6, and IFN-γ in BLM-treated mice. The viability of lung fibroblasts was also reduced, and Bcl-2-associated X protein and cleaved caspase-3 were upregulated after CH treatment in BLM-treated mice. In addition, CH treatment in BLM-treated mice significantly increased levels of cytoplasmic β-catenin but decreased its expression in the nucleus.Conclusion: Administration of CH alleviated BLM-induced PF by inhibiting lung fibroblast proliferation and nuclear translocation of β-catenin. Thus, this study provides a potential therapeutic strategy for PF. Keywords: Chrysophanol, Bleomycin, Pulmonary fibrosis, Hydroxyproline, E-cadherin


2001 ◽  
Vol 37 (2) ◽  
pp. 119-127 ◽  
Author(s):  
RG Lobetti ◽  
R Milner ◽  
E Lane

Five dogs presented with chronic and progressive pulmonary illness characterized by progressive dyspnea, exercise intolerance, and significant inspiratory crackles on auscultation. Radiographically, there was a widespread and diffuse interstitial lung pattern with varying degrees of bronchial involvement. Histopathological changes included thickened alveolar septa, interstitial fibrosis, and pneumocyte hyperplasia. Based on the clinical, radiographic, and histopathological changes, a diagnosis of idiopathic pulmonary fibrosis was made. Idiopathic pulmonary fibrosis is a chronic disease characterized by inflammation and fibrosis of the pulmonary interstitium and peripheral airspaces, which has been poorly characterized in the dog.


2020 ◽  
Vol 32 (4) ◽  
pp. 621-625
Author(s):  
Miguel F. Carrillo ◽  
Deborah Kemper ◽  
Leslie W. Woods ◽  
Francisco R. Carvallo

A 22-y-old American Quarter Horse gelding was presented with a history of chronic progressive respiratory problems and a diffuse pulmonary nodular pattern in thoracic radiographs. The horse was euthanized, and 4 formalin-fixed samples of lung were submitted for histopathology. There were multifocal areas of marked thickening of alveolar septa as a result of proliferation of myofibroblasts embedded in fibromyxoid matrix (interpreted as “Masson bodies”), focal areas of fibrosis, and numerous papillary projections of connective tissue into bronchioles. A diagnosis of organizing pneumonia was reached. No etiology was found for this lesion. It is important to consider causes of chronic interstitial pneumonia with fibrosis in horses other than equid herpesvirus 5, such as complicated viral or bacterial pneumonia or chronic toxicoses.


PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e76451 ◽  
Author(s):  
Ragini Vittal ◽  
Elizabeth A. Mickler ◽  
Amanda J. Fisher ◽  
Chen Zhang ◽  
Katia Rothhaar ◽  
...  

1989 ◽  
Vol 67 (5) ◽  
pp. 1930-1940 ◽  
Author(s):  
E. H. Oldmixon ◽  
J. P. Butler ◽  
F. G. Hoppin

To clarify the mechanics of alveolar parenchyma, we undertook a stereological and topological study in perfusion-fixed canine lungs of the borders of alveolar septa. We defined the principal borders as those along which one septum 1) joins two others (J), 2) joins one other at a distinct angle (B), or 3) joins no other structure (E). E and B borders are invariably reinforced with heavy connective tissue cables; J borders are not. Relative net lengths, determined from the number of traces per section area, were J, 45%; E, 19%; and B, 25%. These were remarkably constant over 10 canine lobes (5 animals, 4 volumes). Parenchyma, then, departs from the simple models that comprise only Js and Es. Bs are important; their net length exceeds that of Es. With lobe deflation, E shortened somewhat more than required to maintain geometric similarity, suggesting that the alveolar duct contracted disproportionately. A three-dimensional reconstruction was made from serial sections, and individual border segments were followed through the reconstruction. Typical lengths of individual J, B, and E borders were nearly equal. To characterize how the network of borders were interconnected, we counted the nodes at which they meet by class, e.g., EBE for the meeting of one B, two Es. The most common are JJJJ, 26%; EEEJ, 10%; EBJ, 24%; EBE, 8%; BBJJ, 12%. If parenchyma were constructed only from free-standing entrance rings and septal junctions, only JJJJ and EEEJ would be anticipated. The presence of EBJ, EBE, and BBJJ underscores parenchymal complexity. Only 7% of septa examined were bordered entirely by Js. Connective tissue cables were not confined to the alveolar duct's lumen but often extended to the primary septa at the periphery of the ductal unit. They rarely linked adjacent alveolar ducts; only 1 in 200 cable segments crossed from one duct to another. These observations support the concept that the parenchyma is an elastic network, characterized in part by a serial mechanical linkage from connective tissue cable to septal membrane to cable again.


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