Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophils, in the course of defending the host against microbial invasion, release a potent arsenal of proteins that can potentially damage host tissues. Defensins are major peptides of human polymorphonuclear leukocyte (PMN) granules and are both broadly microbicidal and cytotoxic to several tumor cell lines. To determine whether these peptides could play a role in neutrophil-mediated lung injury, we examined the cytotoxicity of defensins and other PMN granule proteins in a chromium release assay with human lung-derived cell lines MRC-5 (lung fetal fibroblast), A549 (lung adenocarcinoma with features of alveolar epithelium), and primary cultures of human umbilical vein endothelial cells (HUVEC). Crude fractionation of an acid extract of human PMN granules yielded four fractions A-D. Only fraction D (containing mostly defensins) was significantly cytotoxic to all three target cells. In contrast, fraction A (containing myeloperoxidase and lactoferrin) and fraction C (containing lysozyme) had little effect, and fraction B (containing chiefly cathepsin G and elastase) was only injurious to endothelial cells. The cytotoxicity of whole PMN granule extracts on pulmonary epithelial and fibroblast targets could be completely accounted for by their defensin content. Fraction D- and defensin-mediated cytotoxicity was concentration dependent, required at least 10 to 12 h to become manifest, and was inhibited by serum. The role of these peptides in lung damage during acute and chronic inflammation deserves further study.
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PMID:Direct cytotoxicity of polymorphonuclear leukocyte granule proteins to human lung-derived cells and endothelial cells. 229 76

Eight cases of myelosarcoma without acute leukaemia at time of diagnosis were reviewed and biopsies were immunostained using antibodies reacting with myeloid/monocytic markers. Initial tumour location included lymph nodes, paranasal sinuses, nasopharyngeal and/or orbital regions and other extranodal locations. Three cases developed acute myeloblastic leukaemia within 1-9 months. Diagnosis was correct in four of the cases, in the other cases a non-Hodgkin's lymphoma was initially diagnosed. Morphological examination showed a blastic but variable appearance of the tumours. In a few cases cytoplasmic granulation was present. Chloroacetate esterase was present in all cases. In paraffin sections cathepsin G. elastase or lysozyme were present in all cases except one. In frozen material from four of the cases, the myeloid markers CD 11c and CD 33 were present (all cases) and CD 13 and Ki M8 in 3/4 cases.
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PMID:Myelosarcoma without acute leukaemia: immunohistochemical and clinico-pathologic characterization of eight cases. 233 10

The specificity of the basic bactericidal/permeability increasing protein (BPI) of polymorphonuclear leukocytes (PMN) for gram-negative bacteria is attributable to its strong attraction for the negatively charged envelope LPS. The antibacterial activity of PMN homogenates or extracts toward Escherichia coli corresponds to their BPI content and is blocked by anti-BPI IgG, suggesting that BPI action is unaffected by the presence of other PMN proteins. To test if BPI is preferentially bound to E. coli when other antibacterial proteins are present, we have measured binding in buffered (pH 7.5) balanced salts solution of [125I] human BPI to E. coli J5 in the presence and absence of other human PMN granule proteins. BPI binding is saturable with an apparent K = 23 nM and 2.2 million binding sites/cell. While binding of [125I] human BPI is competitively inhibited by human or rabbit BPI, it is only weakly inhibited by myeloperoxidase, lysozyme, or cathepsin G. In contrast, myeloperoxidase binding to E. coli is strongly inhibited by BPI. Moreover, incubation of E. coli with crude extracts of PMN or CML spleen results in near quantitative binding of BPI, identified by silver staining and immunoblotting after SDS-PAGE of the washed E. coli pellet, without recognizable binding of other leukocyte proteins (greater than 98% of added total protein is recovered in supernatant). After addition of 200 mM MgCl2, approximately 80% of bound BPI is released as fully active and pure protein (as judged by SDS-PAGE and HPLC). Thus the selective and reversible binding of BPI in crude PMN extracts to target bacteria provides a one-step "affinity" purification procedure.
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PMID:Preferential binding of the neutrophil cytoplasmic granule-derived bactericidal/permeability increasing protein to target bacteria. Implications and use as a means of purification. 253 11

The heterogeneity in human neutrophil granules was examined by the ultrastructural localization of a series of antigens which have been previously identified with neutrophil granules by either physical separation or biochemical/biological techniques. All samples were prepared by cryofixation and molecular distillation drying (LifeCell Process), a two-step physical method that achieves cryofixation by metal mirror freezing and drying by the controlled, incremental heating of cryofixed samples in an ultrahigh vacuum. After drying, the samples were either exposed to vapor-phase osmium followed by embedment in Spurr resin, or they were exposed to formaldehyde vapor followed by embedment in Araldite resin. An indirect streptavidincolloidal gold procedure was used for immunoelectron microscopy on ultrathin sections. Subcellular ultrastructural morphology of neutrophils prepared by this method was good compared to standard electron microscopic techniques and superior compared to comparable, published electron microscopic cryomethods applied to neutrophils. Immunogold localization of myeloperoxidase, cathepsin G, lysozyme, lactoferrin, beta 2-microglobulin, and CD-15 antigens showed high intensity and specificity of labeling in the intracellular granules. Patterns of labeling varied from antigen to antigen, demonstrating granule heterogeneity both within and among neutrophils. This methodology is useful in the exploration and definition of granule heterogeneity and function.
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PMID:Human neutrophil granule heterogeneity: immunolocalization studies using cryofixed, dried and embedded specimens. 261 53

Patients receiving multiple whole blood transfusions often experience adverse clinical symptoms caused by leukocytes. In the present study, the efficacy and safety of a polyester filter for leukocytes (Sepacell R-500) was evaluated. Donor units of whole blood and red cell concentrate stored for varying lengths of time were filtered. Emphasis was placed on humoral parameters indicative of release and/or activation reactions of granulocytes (neutral proteinase elastase, lysozyme, aggregation, chemiluminescence) and erythrocytes (lactate dehydrogenase, plasma haemoglobin). Nonspecific adsorption effects were investigated by plasma protein determinations (albumin, alpha 2-macroglobulin). A complete blood cell count as well as values of haemoglobin and haematocrit were determined. Sepacell R-500 proved to be a highly efficient filter to the leukocyte depletion of blood. Our results of erythrocyte and granulocyte related humoral parameters provided no significant evidence of filtration mediated activation or releasing reactions of clinical consequence.
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PMID:Efficacy and safety of a polyester leukocyte removal filter for whole blood and red cell concentrate filtration. 276 May 69

Rat neutrophils added to 3H-labelled glomerular basement membrane (GBM) treated with rabbit anti-rat GBM antiserum degraded the GBM as judged by the release of 3H-labelled peptides. Cells from female animals promoted a more marked degradation than cells from males. This correlated with measurements of higher levels of elastase in granule fractions from the cells. The subcellular distributions of granule marker enzymes was found not to differ between the sexes. Levels of myeloperoxidase, lysozyme, cathepsin G, alkaline phosphatase, gamma-glutamyltranspeptidase and N-acetyl-beta-glucosaminidase showed no sex-based differences. No alpha-mannosidase could be detected in the cells.
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PMID:Biochemical studies of neutrophils from male and female rats: a differential response to basement membrane treated with nephrotoxic antiserum. 284 4

Ten patients were treated with repeated leukophereses performed one to three times per week for 2-5 weeks. Two of the patients was cleared completely, four exhibited regression of more than one-half of the lesions, and four showed only a slight improvement. The therapy did not markedly affect the granulocyte count in peripheral blood, and the beneficial clinical response was not related to the number of polymorphonuclear leukocytes (PMNs) removed by leukophereses. During therapy, the activities of elastase, cathepsin G, lysozyme, and myeloperoxidase in PMNs were determined by spectrophotometry. PMNs isolated using a Haemonetics 30 blood-cell separator were about 50% deficient in these activities in comparison to cells obtained directly from peripheral blood. Thus, leukopheresis induces a marked degranulation of PMNs. Repeated leukophereses were found to generate significant variations in the activities of circulating PMN granule enzymes and in the levels of acid-soluble proteins. Remission or great improvement were observed in patients who, during therapy, exhibited decreased PMN elastase and cathepsin G activities, whereas a poor clinical response was accompanied by high enzymatic activities.
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PMID:Leukopheresis for treatment of psoriasis: is therapeutical benefit related to reduced activities of neutral proteinases of polymorphonuclear leukocytes? 300 6

Reduced bacterial killing by polymorphonuclear leucocytes has been reported in patients with diabetes mellitus. Whether this is due to reduced content of bactericidal granular proteins has not been determined. We therefore immunochemically measured the content of myeloperoxidase, lactoferrin, lysozyme, cathepsin G and elastase in polymorphonuclear leucocytes from 50 insulin-treated diabetic patients. The peroxidase activity was also measured. Normal contents of myeloperoxidase and lactoferrin as well as normal peroxidase activity were found. The average contents of cathepsin G, elastase and lysozyme were 2.5, 3.2 and 2.6 micrograms/10(6) polymorphonuclear leucocytes, respectively, and thus 14, 45 and 18% higher than the contents of normal polymorphonuclear leucocytes. The results indicate that reduced intracellular killing of bacteria demonstrated in previous studies in diabetic patients does not appear to be related to a reduction in the content of bactericidal proteins.
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PMID:Bactericidal proteins and neutral proteases in diabetes neutrophils. 301 98

A small series of granulocytic sarcomas (GS) or 'chloromas' has been studied by means of conventional histology and immunohistochemistry. The latter was found to be most useful in the diagnosis and characterization of these neoplasms, which are rare in Great Britain. Polytypic antisera to leukocyte elastase and cathepsin G have proved to be most useful, giving intense staining in all cases. These two markers are more specific than muramidase (lysozyme) and alpha 1-antitrypsin, since, unlike the latter two, they do not stain histiocytic cells. The results of staining with two monoclonal antisera, AGF 4.48 and AGF 4.36, are also described. In addition, the clinicopathological details of the seven cases are summarized and the literature is briefly surveyed.
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PMID:An immunohistochemical and clinicopathological study of granulocytic sarcoma ('chloroma'). 352 33

Polymethylmethacrylate (PMMA) membranes with different net electric charges and percentage water contents (anionic 71%, neutral 70%, cationic 75%) were evaluated for their ability to stimulate plasma-free human polymorphonuclear neutrophils (PMN), and compared for potency to cuprophan (Cu), already described as being a potent trigger of PMN. The release of lysozyme, beta-glucuronidase, lactic dehydrogenase (LDH), and the generation of a platelet aggregating activity were studied in the supernatants from plasma-free human PMN incubated with different membranes. The PMN intracellular content of neutrophil cationic proteins (NCP), elastase, and cathepsin G were also studied by immunofluorescence using specific antisera on smears of PMN before and after incubation with each membrane. Only cationic, but not anionic or neutral PMMA induced a marked release of lysozyme (range 20-25% of the sonicated control, assumed as 100%), and beta-glucuronidase (40-43%), and marked depletion of the intracellular content of NCP, elastase, and cathepsin G, suggesting a degranulation process. Platelet aggregating activity was generated and referred to the release of platelet activating factor (PAF) only in the supernatants from PMN incubated with cationic, but not with anionic, or neutral PMMA membranes. These results indicate that modification of the net electric charge can per se turn PMMA, commonly recognized as inert, into a material with marked PMN activating effects, comparable to those of Cu, a highly reactive polymer.
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PMID:In vitro complement-independent activation of human neutrophils by hemodialysis membranes: role of the net electric charge. 358 32


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