Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intratracheal application of Bleomycin (Bleo) in rats induces interstitial pneumonitis followed by progressive fibrosis. As the presence of high levels of acute-phase proteins (= reactants = APR), especially alpha 2-macroglobulin of the rat (alpha 2M), enhances liver fibrosis, we investigated whether this phenomenon also occurs in rats with Bleo-induced lung fibrosis. The experiments showed that this is the case; lung fibrosis assessed by measuring hydroxyproline, hexosamine, and prolyl-4-hydroxylase was enhanced when just before Bleo application an acute-phase reaction was induced. This effect can be explained by the inhibitory effect of alpha 2M on collagenase. The experiments showed a significant positive correlation between alpha 2M and parameters of fibrosis. This is especially the case in the third week after Bleo application. Bleo itself does not induce a strong acute-phase reaction, notwithstanding the pneumonitis during the first weeks. The increased fibrosis is accompanied by progressive ventilatory disturbances demonstrated by high arterial pCO2 and low pO2. In patients undergoing Bleo treatment, varying levels of APR can be expected, and this could explain the rapid development of fibrosis in individual cases.
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PMID:Relation between acute-phase proteins and enhanced bleomycin-induced pulmonary fibrosis in the rat. 246 73

Osteopontin is a multifunctional matricellular protein abundantly expressed during inflammation and repair. Osteopontin deficiency is associated with abnormal wound repair characterized by aberrant collagen fibrillogenesis in the heart and skin. Recent gene microarray studies found that osteopontin is abundantly expressed in both human and mouse lung fibrosis. Macrophages and T cells are known to be major sources of osteopontin. During lung fibrosis, however, osteopontin expression continues to increase when inflammation has receded, suggesting alternative sources of ostepontin during this response. In this study, we demonstrate immunoreactivity for osteopontin in lung epithelial and inflammatory cells in human usual interstitial pneumonitis and murine bleomycin-induced lung fibrosis. After treatment with bleomycin, osteopontin-null mice develop lung fibrosis characterized by dilated distal air spaces and reduced type I collagen expression compared with wild-type controls. There is also a significant decrease in levels of active transforming growth factor-beta(1) and matrix metalloproteinase-2 in osteopontin null mice. Type III collagen expression and total collagenase activity are similar in both groups. These results demonstrate that osteopontin expression is associated with important fibrogenic signals in the lung and that the epithelium may be an important source of osteopontin during lung fibrosis.
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PMID:Altered bleomycin-induced lung fibrosis in osteopontin-deficient mice. 1497 30

Bronchoalveolar lavage (BAL) is a technique that samples the inflammatory cells from distal airways and alveoli; however, it is unclear whether or not cellular profiles in the BAL fluid reflect the cellular components of the lung parenchyma in interstitial lung disease (ILD). The aim of this study is to compare immunophenotypes of lymphocytes between BAL fluid and human lung tissue from patients with ILD. Fourteen consecutive patients with ILD who underwent BAL and surgical lung biopsy were enrolled. The diagnosis of ILD was confirmed by the presence of clinical symptoms and impaired respiratory function and on high-resolution computed tomography (CT) of the chest. Mononuclear cells in BAL were immunophenotyped for the expression of CD3, CD4, CD8, CD19, CD45, and CD103 by flow cytometry. Lung tissue obtained by surgical biopsy was digested with collagenase and then centrifuged to extract parenchymal cells. Isolated cells were also immunophenotyped for the same CD expression. Frequencies of positive cells were compared statistically between BAL and different lobes. Seven out of 14 patients were diagnosed clinically as suffering idiopathic interstitial pneumonia. Frequency of CD19+ cells from BAL was significantly lower than that from the upper/middle lobes (P < 0.05). Frequency of CD103+ cells from BAL was significantly higher than that from the upper/middle lobes and the lower lobe (P = 0.01 and P < 0.05, respectively). Comparison between different lobes demonstrated that the frequency of CD4+ cells from the upper/middle lobes was significantly lower than that from the lower lobe (P < 0.05). The results suggest that lymphocyte immunophenotype profiles from BAL may not reflect those in the inflammatory tissue of ILD.
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PMID:Differences in lymphocyte profile between BAL fluid and human lung tissue from patients with interstitial lung disease. 1905 6