Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagenases in bronchoalveolar lavage fluid (BALF) of patients with bronchiectasis and healthy subjects were characterized using specific functional and immunologic assays. The BAL fluid contained interstitial collagenase and collagenolytic proteinases of bacterial origin. Collagenase activities, obtained after organomercurial activation, correlated with the severity of bronchiectasis. In severe cases, collagenase activities were 3.5 x 10(-7) IU/L/48 h or 4.8 x 10(-6) IU/g/48 h (p < 0.01), in moderate ones 1.74 x 10(-7) IU/L/48 h or 3.35 x 10(-6) IU/g/48 h (p < 0.05), and in mild cases 0.32 x 10(-7) IU/L/48 h or 0.7 x 10(-6) IU/g/48 h (p < 0.05). The corresponding activities in healthy control subjects were 0.08 x 10(-7) IU/L/48 h or 0.13 x 10(-6) IU/g/48 h. The cellular origin of interstitial collagenase was assessed with doxycycline inhibition test utilizing the differential sensitivity of fibroblast-type collagenase/MMP-1 (IC50 = 280 microM) and neutrophil-type collagenase/MMP-8 (IC50 = 26 microM) to the anticollagenolytic, nonantimicrobial doxycycline action. Interstitial collagenase, contained in BALF, was totally inhibited by 100 microM of doxycycline. It can therefore be concluded that most of mammalian collagenase presented in inflamed fluid of bronchiectasis originated from neutrophils. The molecular forms of neutrophil-type collagenase/MMP-8 were confirmed and analyzed by Western-blot, which showed evidence of the proteolytic conversion of the latent 85-kD MMP-8 proenzyme species into active 65-kD molecular weight species. These findings strongly suggest involvement of proteolytic activation pathway of proMMP-8, especially in severe and moderate forms of bronchiectasis. Furthermore, collagenolytic proteases of bacterial origins may also participate in tissue destruction of the lung.
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PMID:Human neutrophil collagenase (MMP-8), identified in bronchiectasis BAL fluid, correlates with severity of disease. 778 60

Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix in interstitium resulting in respiratory failure associated with inflammation showing mainly neutrophil (PMN) recruitment. The turn over of extracellular matrix is partially regulated by proteases such as metalloproteinases (MMPs) and their inhibitors (TIMPs). We investigated the impact of PMN depletion on the MMP/TIMP-1 imbalance and the development of fibrosis in mice induced by bleomycin (0.3 mg/mouse). Administration of 200 microL of rabbit anti-mouse PMN antibody i.p. blunted the neutrophil influx detected in BAL and in whole blood one day after bleomycin administration. At day(14), hydroxyproline content was increased both in anti-PMN treated and control mice, without any difference between groups. At day one, bleomycin elicited a raise in pro-MMP-9 level in BAL that was significantly attenuated in anti-PMN depleted mice, whereas TIMP-1 and MMP-2 release were similar in both groups at day(1) and day(14). Higher RNA levels were observed in PMN-treated mice at day(1) for MMP-9 and MMP-2 and at day(14) for MMP-2 only. At day(14), bleomycin elicited a raise of TIMP-1 protein and RNA levels regardless of anti-PMN treatment, whereas MMP-9 returned to basal level. Bleomycin enhanced MMP-8 level in BAL at day(14) only for the control group. The amount of MMP-8 was more important in BAL from anti-PMN treated mice than in control mice at day(1) and day(14). PMN-depletion and the associated modifications in pro-MMP-9/TIMP-1 imbalance in lung during the early inflammatory phase do not alter susceptibility to bleomycin-induced pulmonary fibrosis.
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PMID:Influence of early neutrophil depletion on MMPs/TIMP-1 balance in bleomycin-induced lung fibrosis. 1749 92