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)

The antibacterial activity of a myeloperoxidase (MPO)-glucose oxidase system was found to be greatly increased by granulocyte elastase, present in azurophil granules of human neutrophils. The MPO-H2O3-mediated killing of both Escherichia coli and Staphylococcus aureus was potentiated by granuocyte elastase at an acid pH, whereas at pH 7.4 only killing of E. coli was potentiated. The potentiating effect of elastase was not dependent on the enzymatic properties of the protein since it was not abolished by heating, which destroys the enzymatic activity. A peptide chloromethyl ketone elastase inhibitor abolished both elastolytic activity and the pctentiating effects on MPO-H2-O2-mediated bacterial killing. The antibacterial activity of chymotrypsin-like cationic protein of human neutrophils was also potentiated by elastase. Other degradative enzymes isolated from human granulocytes, e.g., collagenase and lysozyme, did not potentiate MPO-H2O2-mediated or cationic protein-dependent bacterial killing. The present study indicates that a neutrophil constitutent, elastase, which is not microbicidal by itself, can initiate sublethal changes that render some microorganisms more susceptible to the action of microbicidal agents like MPO and chymotrypsin-like cationic protein.
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PMID:Microbicidal mechanisms of human granulocytes: synergistic effects of granulocyte elastase and myeloperoxidase or chymotrypsin-like cationic protein. 1 11

Extracts of specific granules and azurophil granules from human neutrophils were tested for their bactericidal activity against various lipopolysaccharide mutants of Salmonella typhimurium LT-2. Three purified granule populations, one specific and two azurophil, were obtained by isopycnic centrifugation of homogenized neutrophils. Each was extracted with 0.2 M acetate buffer (pH 4), and the extracts were dialyzed against phosphate-buffered saline (pH 7) to remove acetate. These extracts contained >/=84% of the lysozyme, lactoferrin, or myeloperoxidase initially present in the whole granules. The S. typhimurium mutants possessed Ra, Rc, Rd(1), Rd(2), or Re lipopolysaccharide. As the carbohydrate content of the lipopolysaccharide decreased, the bacteria became increasingly more susceptible to the bactericidal activity of all granule extracts. Bactericidal activity of the extracts was in the order: mixed (azurophil + specific) >/= azurophil >> specific. Specific granules were bacteriostatic for S through Rd(2) bacteria. They were bactericidal only for the Re mutant. Both azurophil granule populations were equally bactericidal. Extracts boiled for 30 min retained none of their bactericidal activity for any of the bacteria; however, they remained bacteriostatic for the deep rough (Rd(2), Re) mutants. Bactericidal activity was dependent upon pH, in that mixed and azurophil granule contents killed the smooth parent and Ra mutant best at pH 5, the Rc and Rd(1) mutants to the same degree at pH 5 to 8, and the deep rough mutants (Rd(2) and Re) best at pH 8. Specific granule contents were most bacteriostatic for S through Rd(2) bacteria at pH 5 and killed the Re mutant only at pH 8. Thus, as the S. typhimurium lipopolysaccharide content decreased, the bactericidal pH optimum increased. Killing by all extracts was dependent upon incubation temperature, with almost no bactericidal or bacteriostatic activity observed when bacteria and granule fractions were incubated on ice (2 degrees C) and plated immediately. Intermediate killing was observed at 22 degrees C. If bacteria were incubated with granule extracts at 2 degrees C, washed free of extract, suspended in medium without extract, and reincubated at 37 degrees C, killing was observed. This suggested that a component(s) of the extracts was sticking to the bacteria at 2 degrees C but killing only at 37 degrees C.
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PMID:Bactericidal activity of specific and azurophil granules from human neutrophils: studies with outer-membrane mutants of Salmonella typhimurium LT-2. 2

A transplantable myelogenous leukemia of an inbred Wistar/Furth rat has been established in tissue culture and cloned. The resulting transplantable leukemia line demonstrates in vitro doubling time of 20 hr, colony-forming efficiency of 5% in liquid and methylcellulos-containing medium, and a saturation density of 3.0 x 106 cells/sq cm in liquid medium. Following intraperitoneal inoculation, newborn rats developed solid tumors, ascities, and leukemia with ld50 of5 x 103 cells and mean latency of 60 days. The tumor cell morphology was consistent with that of acute myelogenous leukemia. Histochemical staining for myeloid enzymes revealed no evidence of myeloperoxidase, esterase, or leukocyte alkaline phosphatase; however, fluorescent antibody staining for lysozyme was markedly positive. Serum, urine, and ascitic fluid from rats with transplanted leukemia also contained elevated levels of lysozyme. There was no detectable type-CRNA virus production by this cell line after as long as 100 days in vitro. This inbred rat myelogenous leukemia should provide a useful model for studies of chemotherapy and immunoltherapy of human acute myelogenous leukemia.
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PMID:Acute myelogenous leukemia of the Wistar/Furth rat: establishment of a continuous tissue culture line producing lysozyme in vitro and in vivo. 4 87

Granulocytes from the peripheral blood of normal subjects and a patient with hereditary myeloperoxidase deficiency were homogenized in 0.34 M sucrose. A granule-rich fraction, prepared by sedimentation at 27,000 x g for 20 min, contained components that killed C. parapsilosis in vitro. These were extractable with 0.01 M citric acid and were shown by micropreparative polyacrylamide electrophoresis to be multiple. The candidacidal activity of these neutrophil components was heat stable and they were somewhat more active at pH 5.0 than at pH 7.0. When rabbit or guinea pig heterophils were obtained from sterile peritoneal exudates and similarly fractionated, they also were found to contain components that killed C. parapsilosis in vitro. These were primarily associated with a group of lysosomal cationic proteins lacking direct counterpart in human neutrophils. Among the candidacidal components of the human neutrophil was a protein, more cationic than lysozyme, that exhibited naphthol-ASD acetate esterase activity.
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PMID:Nonoxidative fungicidal mechanisms of mammalian granulocytes: demonstration of components with candidacidal activity in human, rabbit, and guinea pig leukocytes. 4 98

We used immunofluorescent microscopy to characterize the abnormal granules in neutrophils from five patients with Chediak-Higashi disease. Monospecific antiserums to the azurophilic markers myeloperoxidase, elastase, cathepsin G and lysozyme, and to the specific granule markers lactoferrin and lysozyme, were labeled with fluorescein and rhodamine and were used to demonstrate two antigens in the same cell simultaneously. The abnormal granules in Chediak-Higashi neutrophils contained both azurophilic and specific granule markers. Normal-appearing lactoferrin-positive granules were also present, but normal azurophilic granules were not seen. Analysis of bone-marrow samples from two of these patients suggested that the abnormal granules were formed during granulocyte maturation by the progressive aggregation and fusion of normally formed azurophilic and specific granules. These results are consistent with a membrane abnormality or a defect of microtubular function leading to inappropriate granule fusion, and suggest that the granular abnormality is more generalized than previously appreciated.
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PMID:Immunocytochemical identification of azurophilic and specific granule markers in the giant granules of Chediak-Higashi neutrophils. 7 4

Rhesus monkey (Macaca mulatta) neutrophils were shown to contain the azurophilic granule maker enzymes myeloperoxidase and beta-glucuronidase but were deficient in the specific granule markers alkaline phosphatase (AKP) and lysozyme. Isopycnic centrifugation of leukocyte homogenates on linear sucrose gradients resulted in cosedimentation of myeloperoxidase and beta-glucuronidase with an equilibrium density of 1.18. After an intravenous inoculation of monkeys with Salmonella typhimurium AKP activity became marked, whereas that of beta-glucuronidase decreased and myeloperoxidase remained unchanged. Lysozyme was undetected throughout the course of the experiment, but was present in oil-induced peritoneal macrophages and peripheral mononuclear cells. The induced AKP exhibited partial latency and had an equilibrium density of 1.15. It is unclear, however, whether the induced AKP is associated with specific granules or cytoplasmic membranes. Hence, while these data are consistent with the presence of azurophilic granules in polymorphonuclear neutrophils from infected monkeys, the presence of specific granules in polymorphonuclear neutrophils of both uninfected and infected monkeys remains moot.
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PMID:Characterization of monkey peripheral neutrophil granules during infection. 17 Feb 8

The ingestion, bactericidal activity and metabolism of isolated mature neutrophil leucocytes during phagocytosis was studied in 17 patients with chronic granulocytic leukaemia (CGL) with the simultaneous use of normal controls. Seven patients had received no treatment and the others had been treated previously with Busulphan. The phagocytic indices for killed yeast cells did not differ from those of the controls. A diminished bactericidal activity against E. coli was found in nine CGL cases. The bactericidal capacity closely correlated with the degree of leucocytosis since patients with a WBC count of 90 000/mul or higher with one exception showed decreased bactericidal activities while patients with WBC counts below 90 000/mul with two exceptions showed normal bactericidal activities. The [I-14C]-glucose oxidation during phagocytosis was increased in four patients and decreased in three patients. Some correlation was found between abnormally high or low [I-14C]glucose oxidation and diminished bactericidal activity. The intracellular iodination reaction during phagocytosis was decreased in 10 cases while the extracellular iodination was increased in six cases and decreased in one case. The data for granulocyte iodination did not correlate with WBC count, bactericidal capacity or [I-14C]glucose oxidation. The time course for the bactericidal activity and granulocyte iodination seemed to deviate from the controls indicating a slow initial ingestion and/or degranulation phase. The CGL granulocyte content of myeloperoxidase was normal or increased, the lysozyme content was decreased in half of the cases while the amount of antibacterial cationic proteins was increased, normal or low. The present findings indicate a variety of abnormalities in the mature CGL granulocyte, which are not closely interrelated.
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PMID:Granulocyte function in chronic granulocytic leukaemia. I. Bactericidal and metabolic capabilities during phagocytosis in isolated granulocytes. 17 9

The functional significance of granule enzymes in polymorphonuclear leukocytes (PMN) is not fully understood because of the multiplicity of the enzymes and the rare occurrence of deficiencies in man. In order to select appropriate laboratory animals for functional studies, a phylogenetic comparison of enzyme levels in animal and human PMN was undertaken. Neutrophils were obtained from a variety of laboratory animals and man; the activities of alkaline phosphatase, lysozyme, myeloperoxidase, and beta-glucuronidase were determined by histochemical and analytical techniques. Marked interspecies differences in enzyme activity were found; many species were deficient in alkaline phosphatase or lysozyme. Differences in pH optima and metal requirements of alkaline phosphatase were not of sufficient magnitude to explain the variations of this enzyme.
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PMID:Granule enzymes of polymorphonuclear neutrophils: A phylogenetic comparison. 17 39

In 31 patients, covering a wide range of blood neutrophil counts and turnover rates, the plasma concentrations of myeloperoxidase and lactoferrin have been measured with radioimmunoassays and compared to neutrophil kinetic parameters, measured with DF32P-labeled neutrophils. It was found that the plasma concentrations of both proteins correlated significantly with the total number of neutrophils in the blood (TBGP=total blood granulocyte pool) as well as with the neutrophil turnover rate (GTR=granulocyte turnover rate), which is evidence that neutrophilic granulocytes are the main suppliers of myeloperoxidase and lactoferrin to the plasma. In contrast to the previously demonstrated better relationship between the GTR and plasma lysozyme, a protein also originating in neutrophil granules, both myeloperoxidase and lactoferrin correlated better with the TBGP. These differences may reflect differences in the mode of release of intragranular proteins from neutrophils to the plasma. The correlation of the plasma lactoferrin concentration with the TBGP was so good as to suggest its use in the clinical assessment of the TBGP.
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PMID:Plasma myeloperoxidase and lactoferrin measured by radioimmunoassay: relations to neutrophil kinetics. 17 93

The granulocytes of a patient with generalized pustular psoriasis (GPP) were found to have impaired ability to fix iodine after ingestion of yeast particles. Since hexose monophosphate shunt (HMS) activity was increased and the contents of 3 other lysosomal enzymes, beta-glucuronidase, N-acetyl-beta-glucosaminidase and lysozyme, were within normal range, the impaired iodination appeared to be due to a selective defect of myeloperoxidase (MPO) activity within the phagocytic cells. The deficient iodination was accompanied by a decreased intracellular killing of E. coli and C. albicans. Since hexose monophosphate shunt activity was enhanced and azide and cyanide inhibited the intracellular killing of E. coli only moderately, the patient's granulocytes may possess azide- and cyanide-resistant, MPO-independant microbicidal systems coupled to the oxidative metabolism. Assessment of granulocyte iodination and enzyme contents of the relatives of the patient revealed no hereditary transmission. Since GPP is characterized by the development of subcorneal pustules containing granulocytes, the MPO-deficiency may be the cause of or enhance the development of the disease.
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PMID:Function of granulocytes with deficient myeloperoxidase-mediated iodination in a patient with generalized pustular psoriasis. 17 20


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