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 process of connective tissue breakdown in chronic otitis media is described in the context of recent advances in our understanding of collagen degradation and bone resorption. The significance of the initial step in collagen breakdown, brought about by the action of a specific collagen dissolving enzyme is emphasized in terms of recent studies in other chronic inflammatory diseases characterized by connective tissue breakdown. Bone resorption, a characteristic feature of chronic otitis media, requires the breakdown of collagen, which comprises over 90 percent of bone protein. Evidence in support of collagenase in bone resorption from adjacent tissue (in this case, inflammatory connective tissue) would require identification of the enzyme in cells involved in the inflammatory process adjacent to the resorbing bone. Collagenase was found localized in frozen sections of canal wall skin, middle ear granulation and in cholesteatoma by a specific binding of the enzyme with an antiserum produced against purified human skin collagenase. The antigen antibody complex was labelled with fluorescein. Collagenase appeared in the subepithelial connective tissue of cholesteatoma, granulation tissue from the middle ear and the dermis of canal skin; but was not seen in the keratin layer, epithelium or the epidermal appendages. The enzyme appeared within certain fibroblasts, macrophages and endothelial cells of capillary buds. Collagenase enhanced by chronic inflammation attacks the intact collagen molecule, making it susceptible to further digestion by other proteases that are also products of inflammation. This process brings about resorption of connective tissue and bone.
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PMID:Localization of collagenase in human middle ear cholesteatoma. 19 5

Recent investigations have indicated that cytokines such as tumor necrosis factor-alpha (TNF-alpha) play a potential role in the bone resorption associated with inflammatory diseases. In this immunoperoxidase study, TNF-alpha was localized in mononuclear cells, macrophages, fibroblasts, osteoblasts, and osteoclasts adjacent to bone resorption areas in both human and experimental middle ear cholesteatomas. In vitro, TNF-alpha stimulated monocytes to form multinucleated cells that demonstrate tartrate-resistant acid phosphatase activity, a marker enzyme for osteoclasts. These multinucleated osteoclast-like cells induce resorption of devitalized bone. The extent of bone resorption was increased by the co-cultures of osteoblasts and osteoclasts in the presence of TNF-alpha, suggesting that cell to cell interaction plays a significant role in bone resorption. Moreover, TNF-alpha was capable of stimulating macrophages to produce acid phosphatase and collagenase, and osteoblasts to produce prostaglandin E2 and collagenase. These chemical mediators have been known to lead to bone resorption. Our findings suggest that TNF-alpha may play an important clinical role in the destructive process of cholesteatoma.
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PMID:The role of tumor necrosis factor-alpha in bone resorption of cholesteatoma. 165 Jan 49

Endotoxin levels and lysosomal protease (collagenase, cathepsin B, and lysozyme) activity were measured in 104 middle ear effusions (MEEs) from patients with otitis media with effusion (OME). The MEE samples were classified into four groups: pediatric serous, mucoid, and acute, and adult serous. Endotoxin levels and lysosomal protease activity in MEEs were significantly different in the following order: adult less than serous less than mucoid less than acute groups, indicating that both endotoxin and lysosomal proteases are more closely related to the pathogenesis of pediatric chronic OME than to adult OME. In pediatric serous and mucoid effusions, endotoxin level had a significant correlation with activity of the lysosomal proteases. In conclusion, endotoxin enhances leukocyte infiltration into the middle ear, and lysosomal proteases released from leukocytes damage the middle ear mucosa and thereby prolong mucosal inflammation, which may be responsible for delayed recovery from acute OME.
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PMID:Endotoxin and lysosomal protease activity in acute and chronic otitis media with effusion. 215 54

Hydrolytic activity of various lysosomal proteases--elastase, collagenase, and cathepsins B and H--were measured in 125 middle ear effusions from patients with chronic (serous and mucoid) and acute otitis media with effusion (OME). The levels of cathepsin B activity and alpha-2-macroglobulin during the course of clinical therapies (myringotomy and tympanostomy tubing) were analyzed in 10 chronic OME cases where follow-up evaluation was possible. It is found that the level of lysosomal protease activity (elastase, collagenase and cathepsin B) was higher in acute OME than that in chronic OME; the hydrolytic activity of cathepsin B in middle ear effusions could be used as an indicator to reflect the level of lysosomal proteases activity in the middle ear; in chronic OME, inflammatory reaction including lysosomal protease activity of the middle ear mucosa at the time of the first myringotomy appeared to be more active than that at the time of the final myringotomy, but less than that in acute OME; and the proteolytic damage of lysosomal thiol proteases to the middle ear mucosa, which may be related to the chronicity of OME, could be reduced by both therapeutic myringotomy and tympanostomy.
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PMID:Kinetics of lysosomal protease activity in human otitis media with effusion. 244 31

Collagenolytic enzyme activity has been demonstrated in middle ear effusions from patients suffering from otitis media with effusion. Collagenase activity was characterized using different biochemical techniques. Various chemical and physical parameters were titrated for optimal enzyme activity. Bivalent cations activated the enzyme with Ca2+ as the most potent activator. Chelators such as EDTA reduced the enzyme at low concentrations. The enzyme was found to have a higher specific activity in mucoid effusions than in serous and had characteristics similar to granulocyte derived collagenase from human leukocytes. Possible relationships between the presence of collagenase activity and tissue destruction in the middle ear after otitis media with effusion are discussed. The collagenase activity showed wide ranges within different categories of middle ear effusions.
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PMID:Collagenase activity in middle ear effusions. 300 19

Collagenolytic enzyme activity has been demonstrated in middle ear effusions from patients suffering from otitis media with effusion. Collagenase activity was characterized using different biochemical techniques. The enzyme was found to have a higher specific activity in mucoid effusions and had characteristics similar to granulocyte derived collagenase from human leucocytes.
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PMID:Biochemical characterization of collagenase activity from middle ear effusions. 301 46

Mononuclear phagocytes are cells common in the subepithelial space of the mucosa of the middle ear and in middle ear effusion during an attack of otitis media. Here we review studies to date on biological potentials of aural macrophages in the pathogenesis of otitis media. The origin of aural macrophages may be in the circulating pool of monocytes in the blood, in the pre-existing population of macrophages in the mucosa of the middle ear, in proliferation of macrophages in the middle ear, or in nasopharyngeal and tonsillar tissues. Macrophages demonstrate great phagocytic activity in eliminating tissue-debris, bacteria, and viruses. It seems likely that the secretory products of macrophages--such as lysozyme, components of complement, prostaglandins, collagenase, and other biologically active agents--play an important part in the pathogenesis of otitis media. There is also evidence available that aural macrophages play an important role in the regulation of lymphocytic response to antigens in active otitis media.
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PMID:Aspects of biological potentials of mononuclear cells in middle ear effusions. 639 5

Otitis media has a complex multifactorial pathogenesis, and the middle ear inflammatory response is typified by the accumulation of cellular and chemical mediators in middle ear effusion. However, specific biochemical and immunochemical factors that may be responsible for the severity or chronicity of otitis media have not been identified. Identification of factors involved in chronicity appears to be an essential step in the treatment and ultimate prevention of chronic otitis media. We analyzed 70 effusion samples from patients 1 to 10 years of age who had chronic otitis media with effusion for two cytokines (interleukin-1 beta and tumor necrosis factor alpha) and total collagenase. The highest concentrations of all three inflammatory mediators were found in purulent otitis media, and concentrations were higher in younger than in older patients. Mediator concentrations were similar in samples obtained from patients having their first myringotomy for otitis media with effusion and in those who had had multiple previous myringotomies. The multiresponse star, which incorporates several biochemical parameters in one graphic illustration, may best characterize the complex nature of middle ear inflammation.
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PMID:Determining otitis media severity from middle ear fluid analysis. 817 69

Nine cholesteatomas, seven middle ear granulations and five deep meatal skin specimens were analysed for gelatinase activity at molecular weights corresponding to those of matrix metalloproteinase-1 (MMP-1) using SDS PAGE zymography. Gelatinase activity at 41-43 kDa and 45-47 kDa was investigated. Western blotting was employed using a primary monoclonal antibody to MMP-1 to provide a qualitative assessment of MMP-1. Western blotting was also used with a monoclonal antibody to MMP-3 to discover if MMP-3 gelatinase activity occurring around the molecular weight of MMP-1 may have contributed to the results. A significantly higher expression of activity was recorded in cholesteatoma and middle ear granulations at 45-47 kDa in comparison with deep meatal skin. Western blotting indices were to be present in all of the cholesteatoma specimens tested. Only one of the specimens (cholesteatoma) tested showed any MMP-3 presence.
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PMID:Matrix metalloproteinase-1 in cholesteatoma, middle ear granulations and deep meatal skin: a comparative analysis. 988 4