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

Tissues from seventy-one patients were obtained within one-half hour of biopsy, mastectomy, or reduction mammoplasty and processed for scanning electron microscopy (SEM). Epithelial structures were detected by supravital staining with methylene blue and isolated by microdissection. Mammary lobules and ductules required bacterial collagenase digestion to remove the covering stroma for optimal visualization. Major histopathological categories were compared and correlated with the characteristics observed with methylene blue supravital staining and light microscopy and/or transmission electron microscopy as a function of surface features revealed by SEM. Mammary ducts can be readily distinguished from ductules and lobules by their characteristic surface epithelium. Duct epithelium undergoes a variety of changes in fibrocystic disease (FCD) and in carcinoma. Both apocrine and merocrine secretory activity was observed in the surface epithelium. Proliferation of both epithelial and stromal elements was observed in benign fibroadenomata. Intraductal carcinomas were distinguished by their relative lack of surface microvilli. SEM offers a practical tool in the potential identification of premalignant cells of the human breast epithelium.
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PMID:Diseases of the human breast: selective isolation and exposure of epithelia and their correlative surface features and histopathology. 23 May 74

Cystic fibrosis is associated with an cAMP-regulated channel defect, which has been evidenced in many cell types including B lymphocytes. To document a B-cell dysfunction potentially related to this defect, we studied the in vitro IgG production by lymphocytes from 11 cystic fibrosis patients. B lymphocytes were co-cultured with autologous monocytes and stimulated with Staphylococcus aureus Cowan or with Nocardia-delipidated cell mitogen in the presence of low concentrations of IL2. Cystic fibrosis patients' cells produced amounts of IgG comparable with that of normal and control patients' cells. However, dexamethasone (10(-7) mol l-1) had no effect on the response of cystic fibrosis patients' cells, whereas it enhanced that of the latter two groups. This resistance of cystic fibrosis cells was true with concentrations of dexamethasone up to 10(-6) mol l-1, whereas this agent induced a dose-related enhancement from 10(-8) to 10(-6) mol l-1 in cultures of normal cells. Co-culture experiments showed that cystic fibrosis B lymphocytes themselves are resistant to the effect of dexamethasone. In contrast dexamethasone normally suppressed the anti-CD3 antibody-induced response of cystic fibrosis T cells in the presence of IL2 and the IL1 alpha- or beta-induced collagenase production of cystic fibrosis fibroblast cell lines. Thus cystic fibrosis B lymphocytes exhibit a selective defect which may interfere with the normal interactions between the hormonal and immune systems and may participate in the sensitivity of cystic fibrosis patients to bacterial bronchopulmonary infections.
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PMID:Cystic fibrosis patients' B-lymphocyte response is resistant to the in vitro enhancing effect of corticosteroids. 196 24

In the past 4 yr, 16 adult patients were identified who had accelerated onset of a severe respiratory disorder (usually obstructive in nature) that was clinically distinct from the more commonly encountered chronic obstructive disorders (e.g., chronic bronchitis, emphysema, asthma, bronchiectasis, cystic fibrosis, and alpha 1-antitrypsin deficiency). These patients, termed patients with "bronchiolitis," underwent pulmonary function testing, bronchoscopy with bronchoalveolar lavage (BAL), and open lung biopsy. Although lung biopsy findings varied somewhat among the patients, each biopsy contained a prominent component of bronchiolitis. Pulmonary function testing and BAL were also repeated after 3 months of treatment with oral prednisone (1 mg/kg/day). Initial BAL neutrophil percentages were significantly higher in the bronchiolitis group (54 +/- 10%) than in smokers with chronic bronchitis (3.9 +/- 1.0%) or in normal nonsmoking volunteers (0.8 +/- 0.5%) (p less than 0.01, both comparisons). Eleven of 15 patients with bronchiolitis had significant improvement (greater than or equal to 15% increase in FEV1) in their lung function after prednisone treatment. Furthermore, this "responder" subgroup had a significant reduction in BAL neutrophil percentages after treatment with prednisone (46 +/- 15% to 6 +/- 3%, p less than 0.05). Finally, the neutrophil products collagenase and myeloperoxidase were detected in the BAL fluid of patients with bronchiolitis. These findings suggest a central role for the neutrophil in the pathogenesis of bronchiolitis and emphasize the utility of BAL in the identification of these patients.
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PMID:Bronchiolitis in adults. A reversible cause of airway obstruction associated with airway neutrophils and neutrophil products. 254 26

The tracheal mucosa from a 12-year-old girl was digested with collagenase 4 hr after her death from cystic fibrosis. Forty million viable cells were obtained. The cells, plated at 10(6) per cm2 onto four Nuclepore filters coated with human placental collagen, formed confluent monolayers after 1 day. Their ultrastructure was similar to that of normal human cells. They were studied in conventional Ussing chambers or with intracellular microelectrodes on days 5-7 after plating. The monolayers displayed resistance of 380 +/- 50 omega X cm2 and short-circuit current (Isc) of 1.8 +/- 0.4 microA X cm-2. This resistance is similar to that obtained for dog or normal human monolayers. The Isc is less than normal human (approximately 3 microA X cm-2) or dog (approximately 10 microA X cm-2) cells. The cystic fibrosis cells resembled normal monolayers in that serosal ouabain and mucosal amiloride inhibited Isc, while mucosal ouabain or serosal amiloride had no effect. They differed from normal human or dog cells in that Isc was not inhibited by bumetanide and the stimulation of Isc by isoproterenol or prostaglandin E2 was greatly reduced or abolished. Addition of isoproterenol depolarized apical membrane potential (psi a) and decreased fractional resistance (fR) in normal human and dog but had no effect on psi a or fR in cystic fibrosis cells. Reduction of mucosal chloride from 120 to 5 mM by replacement with gluconate increased fR of dog and normal human monolayers and depolarized psi a by 22 (dog) or 30 (human) mV. In cystic fibrosis monolayers, chloride replacement hyperpolarized psi a by 2 mV and had little effect on fR. These results suggest that the primary defect in cystic fibrosis is reduced apical membrane chloride conductance.
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PMID:Cystic fibrosis decreases the apical membrane chloride permeability of monolayers cultured from cells of tracheal epithelium. 386 25

Recent electrophysiological and pharmacological studies have confirmed previous clinical evidence that the gene defect in cystic fibrosis is strongly expressed in the sweat gland. This has provided a major impetus to efforts to culture the cells of this tissue in order to provide a source of experimental material for molecular studies. Toward this end, eccrine sweat glands were isolated from collagenase treated skin specimens and the secretory coil and the reabsorptive duct separated. Segments of each portion of the gland were transferred to a plastic or collagen substrate and covered with serum-containing or serum-free defined growth media. Epithelial cell outgrowth took place in both media but fibroblast overgrowth occurred in the presence of serum at concentrations as low as 1%. In serum-free medium both secretory and reabsorptive cells formed tightly joined epithelial sheets, first as monolayers and later as multilayers consisting of at least six cell layers. Growth continued for approximately fifteen generations each of about two and a half days. Remarkably large domes or hemicysts with diameters as great as two cm were formed, apparently attesting to the retention of the capacity of the cells to actively transport ions and water. Ultrastructurally, cells which grew out from the secretory coil resembled the fluid secreting clear cells; neither dark cells nor myoepithelial cells were propagated.
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PMID:Culture of sweat gland epithelial cells from normal individuals and patients with cystic fibrosis. 405 13

The virulence of Pseudomonas aeruginosa, which is easily differentiated from the two other most common pseudomonad pathogens, is low. This species primarily causes disease in patients with local anatomic changes or in the immune compromized hosts. A number of bacterial factors are involved in the pathogenesis of the microbe. Surface structures like the glycocalyx-capsular material-is involved in attachment to mucosal surfaces and resistance against phagocytosis and immunolysis of cells. The interference with bacterial components on mucociliar clearance of the bronchial tract have been described. In cystic fibrosis local environmental substances enhancing the production of capsular material have been described and the tendency for colonization of mucoid strains in cystic fibrosis probably is related to these factors. Another general component of gram-negative bacteria is endotoxin, but the toxicity of this cell wall constituent is relatively low in P. aeruginosa. A number of proteolytic enzymes with a probable role in disease have been described: collagenase, fibrinolysin, elastase, caseinase, and gelatinase. A proteolytic enzyme with activity against substances like casein, egg albumin, gluten, and haemoglobin has been described. A component like exotoxin A can produce skin lesions and antibodies produced with toxoid of exotoxin A are protective against this bacterial agent. Enterotoxin has been described based on rabbit intestinal loop preparations, but has not been further characterized and diarrhoea is rarely caused by P. aeruginosa. Haemolytic effect has been caused by a heat labile phospholipase C and by a heat stabile moiety. A leucocidin has been described: this may in part be capsular material. In addition, an exoenzyme S has been suggested as a virulence factor.
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PMID:Pathogenetic factors of Pseudomonas aeruginosa. 679 59

The potential role of neutrophil elastase in causing lung damage and exacerbating the inflammatory response in cystic fibrosis (CF) has received considerable attention. Although another potent neutrophil-derived enzyme, collagenase, is implicated in tissue destruction in several interstitial lung disorders, there has been no reference to this enzyme in CF. The objective of this study was to determine whether neutrophil collagenase is present in active form in CF sputum and, if so, whether it is related to disease severity. High levels of active collagenase were detected in sputum from patients with CF, and the majority of the enzyme present was of neutrophil origin. In a group of 16 patients with CF, negative relations between sputum collagenase activity and Shwachman score (r = -0.55, p < 0.05) and FEV1 (r = -0.59, p < 0.02) were noted, indicating an association between high collagenase activity and severity of disease. A positive correlation was observed between sputum collagenase and elastase activity (r = 0.62, p < 0.05). These results suggest that both neutrophil elastase and collagenase may play a significant role in lung destruction in CF.
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PMID:Neutrophil collagenase in sputum from patients with cystic fibrosis. 808 57

Alpha-1 proteinase inhibitor (A1-Pi) is the main serine proteinase inhibitor found in human plasma and is a potent elastase inhibitor in various tissues, including lung. A1-Pi is expressed and induced in liver during inflammatory responses but can also be produced by epithelial cells. Since hepatocyte A1-Pi production is stimulated by interleukin-6 (IL-6) and other gp130-cytokines, such as leukemia inhibitory factor (LIF) and oncostatin M (OM), we investigated the role of these cytokines in regulating A1-Pi in lung epithelial cells. We show that OM, a monocyte and T cell product, can specifically and potently induce A1-Pi production in lung-derived A549 alveolar (epithelial) cells, as well as in liver-derived HepG2 cells. Both A1-Pi protein (as detected by ELISA and Western blots) and mRNA levels were enhanced 20-fold to 30-fold in A549 cells. OM was also able to stimulate the expression of tissue inhibitor of metalloproteinase-1 in these cells. Interestingly, other members of the IL-6 family (IL-6 and LIF) had little or no effect on A549 cells, and proinflammatory cytokines, such as IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) also had no stimulatory effect on A1-Pi synthesis in A549 cells. Costimulation with IL-1 beta resulted in a decrease in A1-Pi production from OM-stimulated A549 cells. However, IL-6 production was synergistically enhanced. OM was also able to stimulate A1-Pi production from a bronchial epithelial primary cell line, whereas an intestinal epithelial cell line HT29 responded to IL-6 but not OM. These results suggest that lung levels A1-Pi could be derived not only from liver and inflammatory cells but also from epithelial cells, which can be upregulated on stimulation by OM. This may have implications for regulation of local activity of human neutrophil elastase (HNE) in such diseases as emphysema and cystic fibrosis.
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PMID:Oncostatin M, but not interleukin-6 or leukemia inhibitory factor, stimulates expression of alpha1-proteinase inhibitor in A549 human alveolar epithelial cells. 919 1

We report that matrilysin, a matrix metalloproteinase, is constitutively expressed in the epithelium of peribronchial glands and conducting airways in normal lung. Matrilysin expression was increased in airway epithelial cells and was induced in alveolar type II cells in cystic fibrosis. Other metalloproteinases (collagenase-1, stromelysin-1, and 92-kD gelatinase) were not produced by normal or injured lung epithelium. These observations suggest that matrilysin functions in injury-mediated responses of the lung. Indeed, matrilysin expression was increased in migrating airway epithelial cells in wounded human and mouse trachea. In human tissue, epithelial migration was reduced by > 80% by a hydroxamate inhibitor, and in mouse tissue, reepithelialization in trachea from matrilysin-null mice was essentially blocked. In vivo observations and cell culture studies demonstrated that matrilysin was secreted lumenally by lung epithelium, but upon activation or while migrating over wounds, some matrilysin was released basally. The constitutive production of matrilysin in conducting airways, its upregulation after injury, its induction by alveolar epithelium, and its release into both lumenal and matrix compartments suggest that this metalloproteinase serves multiple functions in intact and injured lung, one of which is to facilitate reepithelialization.
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PMID:Matrilysin expression and function in airway epithelium. 976 24

Invasive growth requires degradation of extracellular matrix. Altered expression of matrix degrading enzymes may indicate an increased potential for invasive growth. We determined the expression patterns of matrix-metalloproteinases (MMP)-1, -2, and -3 and of the tissue inhibitors of metalloproteinases (TIMP)-1 and -2 by in situ hybridization with isotopically labeled RNA probes in normal breast tissue (n=6), fibrocystic disease (n=20), five cases of which contained radial scars, lobular carcinoma in situ (CLIS; n=5), ductal carcinoma in situ (DCIS; n=9) and invasive carcinomas (n=24). Only a few cells displayed MMP-1- and MMP-2-specific labeling in normal breast tissue and fibrocystic disease. Noninvasive ductal carcinomas showed elevated MMP-2 transcript levels in peritumor stromal cells in the absence of significant MMP-1 specific signals. In general, compared with adjacent normal breast tissue, a gradual increase of MMP-2 was found in noninvasive to invasive cancers. Invasive ductal and lobular carcinomas displayed co-expression of MMP-1 and MMP-2 by stromal cells, mainly of the invasion front, with high signal intensity particularly in high-grade invasive carcinomas. Tumor cells and peritumor stroma showed low MMP-3 transcript levels, especially in medullary carcinomas. TIMP-1 and -2 transcript levels were increased in invasive carcinomas correlating with the histological grade. These RNA expression patterns suggest an increased invasive potential in breast carcinomas even prior to histologically overt invasive growth.
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PMID:Matrix-metalloproteinases 1, 2, and 3 and their tissue inhibitors 1 and 2 in benign and malignant breast lesions: an in situ hybridization study. 1062 98


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