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)

The symptoms of adult respiratory distress syndrome (ARDS) include dyspnea, tachypnea, hypoxemia refractory to supplemental oxygen and bilateral infiltrations in the chest X-ray. Neutrophils are implicated in the pathogenesis as important effector cells acting by release of mediators. Activation of the complement system has been shown in several studies and can induce lung damage directly in animal models. Proteases and collagenase have been found in elevated concentration in bronchoalveolar lavage fluid, while the amount of protease-inhibitors has been found to be reduced. Arachidonic acid metabolites of the cyclooxygenase and lipoxygenase pathway, such as prostaglandins and leukotrienes, may play a role in the pathogenesis or perpetuation of the disease process. The same holds true for cytokines such as interleukin-1 or tumor necrosis factor. All of them have been found to be elevated either in plasma or bronchoalveolar lavage fluid of ARDS patients. Several lines of evidence implicate oxygen radicals as important mediators of lung damage in ARDS. The therapeutic implications of these new insights into the pathogenesis of ARDS are briefly discussed.
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PMID:[Mediators and ARDS]. 165 27

Chronic elastolytic activity in the lung is currently believed to be a major factor in pathogenesis of emphysema. Collagenase may have similar role in disorganizing lung collagen network, leading to fibrotic lung diseases (FLD). The possible involvement of collagenase in FLD is suggested by: 1) an increase collagenolitic activity in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis or adult respiratory distress syndrome; 2) the accumulation and the activation of cells able to produce collagenases in FLD: fibroblasts, macrophages, neutrophils and eosinophils. However the exact role of collagenase in FLD is still unknown: it could inhibit neocollagen deposition, limiting fibrotic process or lead to further destruction of collagen network. Recent data suggest that genomic macrophage activation (such the proto oncogene c-SIS) may lead to several cellular events: 1) increase number and activation of fibroblasts with collagen synthesis; 2) increase collagenase production resulting of accumulation and activation of fibroblasts, macrophages, neutrophils. So we conclude that such a genomic macrophage activation may be the major factor contributing to the collagen network damage leading to lung tissue fibrosis.
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PMID:[Collagenase and diffuse interstitial pneumopathy]. 285 67

Collagenase activity in the bronchoalveolar lavage (BAL) of patients with adult respiratory distress syndrome (ARDS) was measured against Type I collagen (17 patients) and against Type III collagen (13 patients). Serine protease activity was also measured against Type III collagen (13 patients). Type I collagenase activity was detectable in 12 of 17 and Type III collagenase was detectable in 12 of 13 patients with ARDS. The 10 control subjects had no detectable Types I or III collagenase activity. Total and differential white cell counts were analyzed in the lavage fluid. Although the total counts did not differ between patients with ARDS and control subjects, the percentage of neutrophils was increased more than 25-fold and the percentage of macrophages was reduced almost 10-fold in the ARDS patients. Serial collagenase activity was followed in 1 ARDS survivor. In this patient Type III collagenase activity peaked before the Type I collagenase activity or serine protease activity reached their maximums. Both the latter enzyme activities paralleled the total recoverable cells in the BAL.
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PMID:Collagenase in the lower respiratory tract of patients with adult respiratory distress syndrome. 298 85

The high in-hospital mortality of ARDS has not diminished over the past 10 years, despite improvements in supportive intensive care. Much of the mortality arises from infections, particularly sepsis and pneumonia, and from organ failure, especially kidney failure. The rapid advances in understanding the interlocking pathophysiologic mechanisms of ARDS have not yet been translated into therapeutic trials of new methods for diminishing the injury or for stimulating normal repair. In part, this is because it is difficult to predict which high-risk patients will develop ARDS and then intervene early in the injury process. Patients in whom the risk for ARDS is extremely high have a very high mortality even without ARDS, thereby making efficacy of an early or prophylactic therapy quite difficult to prove. In spite of severe pathologic abnormalities, including fibrosis, early in the course of ARDS, most survivors return to almost normal pulmonary function. The few cases that have been studied with serial biopsies demonstrate resolution of fibrosis. This amazing recovery poses many fascinating questions about how the lung repairs itself. Given the heterogeneous causes of ARDS and the large number of structural, cellular, and biochemical abnormalities described, one can postulate that any one of numerous factors is important in normal repair. Most promising of these are the degree of basement membrane damage, the control of type II cell proliferation and differentiation, the control of collagen synthesis, the anatomic localization of fibrosis, and the control of collagenase action. These interactions of epithelial and mesenchymal tissues probably recreate the process of lung development in the injured adult lung. At a clinical level, the role of oxygen toxicity remains a significant issue. Oxygen acting as an oxidant may be partially responsible for the small airways disease seen in approximately one quarter to one third of survivors. The mortality data stress the need for better ways of preventing and diagnosing lung infections. Better definition of the clinical factors that put survivors at risk for persistent loss of lung function is also needed, and could define a subgroup in which trials of agents designed to improve repair would be most worthwhile. More information about the long-term pathologic course, though difficult to obtain, would also be very important. Perhaps some registry of ARDS survivors would permit closer follow-up and make available more late autopsy pathology when these people die of other causes. The rapid time course of ARDS provides an ideal testing ground for agents designed to either decrease lung injury or stimulate repair.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pulmonary sequelae and lung repair in survivors of the adult respiratory distress syndrome. 333 67

The formation of adducts between methyltetrahydrophthalic anhydride (MTHPA), an important industrial chemical and potent allergen, and collagen from guinea pig lung tissue was investigated. Collagen peptides were obtained from the lung tissue by homogenization, defatting, washing, and digestion with collagenase. In experiments in vitro, lung tissue was exposed to 8.4 mumol (50 microCi) of 14C MTHPA. The amount of adducts was 97 nmol MTHPA/g of wet tissue as determined from the bound radioactivity. In a study in vivo, four guinea pigs were injected intratracheally with 8.4 mumol of 14C MTHPA each. The amount of adducts was 0-1.2 nmol MTHPA/g of wet tissue (determined by bound radioactivity). N epsilon-methyltetrahydrophthaloyl-L-lysine (MTHPL) was synthesized and characterized by NMR, UV, and mass spectrometry (MS). A method to analyze MTHPL, after derivatization with methanol and pentafluorobenzoyl chloride, using gas chromatography-MS was developed. Analysis of Pronase-digested MTHPA-exposed lung tissue showed a concentration of 19 nmol MTHPL/g wet lung in vitro and between 0 and 0.15 nmol MTHPL/g wet lung in vivo. Thus, 20% in vitro and 12-15% in vivo of the bound radioactivity was found as adducts with lysine. These results are a first step toward studies of allergenic epitopes in proteins and methods for biological monitoring of exposure to acid anhydrides.
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PMID:Lysine adducts between methyltetrahydrophthalic anhydride and collagen in guinea pig lung. 748 35