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

The mechanism was studied of the anti-inflammatory effect of oral zinc (114 mg/kg/day of elemental metal, given for 14 days) on the development of the carrageenan-induced paw oedema of the rat, and the impact of in vivo treatment on the activity of neutrophils isolated from the blood of inflamed and non-inflamed animals. The effects of the in vitro incubation with the metal on either non-inflamed or inflamed neutrophils coming from zinc-untreated rats were also examined. It was found that the administration of oral zinc inhibited markedly the process of ex vivo adhesion of the cells obtained from the inflamed rats (an observation confirmed by the in vitro experiments). In vitro release of lysozyme and superoxide anion productions were measured: in the absence of zinc, the 30' of pre-incubation carried out before stimulating with PMA did not influence the cell's reactivity of the non-inflamed neutrophils. It was, on the contrary, capable of significantly reducing that of the inflamed ones. As a consequence, it is quite difficult to properly interpret the data obtained studying the activity of the cells exposed to the metal in vitro.
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PMID:Neutrophil behavior following exposure to in vivo or in vitro zinc in normal and acutely-inflamed rats: studies on lysozyme secretion, superoxide anion release and platelet adhesion. 956 27

Urokinase-type plasminogen activator receptor (UPA-R-CD87) is a GPI-anchored membrane protein which promotes the generation of plasmin on the surface of many cell types, probably facilitating cellular extravasation and tissue invasion. A flow cytometric quantitative analysis of expression levels for UPA-R was performed on fresh blast cells from patients with acute myeloid leukaemia (AML, n = 74), acute lymphoblastic leukaemia (ALL, n = 24), and biphenotypic leukaemia (BAL, n = 3) using two CD87 monoclonal antibodies (McAbs) (3B10 and VIM5). Peripheral blood and bone marrow (BM) cells from 15 healthy adults served as controls. Using 3B10 McAb, UPA-R was expressed (>99%) by blood monocytes, neutrophils, and BM myelomonocytic precursors in controls, whereas resting T and B lymphocytes, and CD34+ cells were UPA-R negative. We also attempted to clarify whether UPA-R has a role in mediating neutrophil functions. Oriented locomotion induced by different chemotaxins and lysozyme release by granules stimulated with fMLP or PMA were significantly decreased when UPA-R was neutralized by CD87 McAb. In contrast, the anti-UPA-R McAb had no effect on superoxide anion generation of normal neutrophils. Blasts from AML showed a heterogenous pattern of expression for the UPA-R McAbs, with reactivity strictly dependent on FAB subtype. The highest UPA-R expression was seen in the M5 group: all patients tested (n = 20) showed strong positivity for the UPA-R McAb whereas only 12% (3/24) of ALL patients were CD87 positive, and 2/3 of BAL patients showed a dim expression for CD87. The number of receptors expressed by blast cells in 6/74 (8.1%) AML patients was higher than those of normal samples: in addition, since co-expression of UPA-R and CD34 was not found in normal haemopoietic cells, it may be postulated that CD87 can be used alone (when overexpressed) or in combination with CD34 for the detection of minimal residual disease. Results also indicated that patients with UPA-receptors >12 x 10(3) ABC/cell, irrespective of FAB subtype, had a greater tendency for cutaneous and tissue infiltration and a higher frequency of chromosome abnormalities, thus suggesting the concept that cellular UPA-R content positively correlates with the invasive potential of AML cells. The combination of higher UPA-R positivity, abnormalities of chromosome 11, and M5 FAB morphology may identify a peculiar subset of AML, characterized by a more aggressive clinical course.
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PMID:Expression and functional role of urokinase-type plasminogen activator receptor in normal and acute leukaemic cells. 979 97

Recombinant human interleukin-11 (rHu-IL-11) is a multifunctional cytokine with thrombopoietic activity and demonstrated clinical efficacy in treating chemotherapy-induced thrombocytopenia. rHu-IL-11 also exhibits anti-inflammatory activity and is currently in clinical trials for the treatment of several inflammatory diseases. As neutrophils are involved in both innate immunity and an acute inflammatory response, the effect of rHU-IL-11 on the function of human peripheral blood neutrophils in vitro was examined. rHu-IL-11 was not cytotoxic and did not induce superoxide anion production or the release of granular enzymes from resting neutrophils. Phagocytosis and chemotaxis were unaffected. rHu-IL-11 treatment did not block the response of neutrophils to stimulation. Pretreatment with rHu-IL-11 did not reduce production of IL-8 following activation with lipopolysaccharide (LPS) or zymosan A particles. Pretreatment with rHu-IL-11 did not affect the release of lysozyme and beta-glucuronidase in response to A23187 or PMA-stimulated production of superoxide anion. These results indicate that rHu-IL-11 does not directly modulate key functions of neutrophils in vitro.
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PMID:Recombinant human interleukin-11 does not affect functions of purified human neutrophils in vitro. 980 25

The lipophilic aglycone 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphalin) isolated from the aerial flowering parts of Helichrysum picardii Boiss. & Reuter (Asteraceae) was tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in stimulated rat peritoneal leukocytes, and for its effects on leukocyte granular enzyme release, cell viability and interactions with reactive oxygen species. Gnaphalin dose-dependently inhibited generation of the cyclo-oxygenase metabolite thromboxane B2 (IC50 = 39.9 +/- 3.9 microM), and of the 5-lipoxygenase metabolite leukotriene B4, although the potency was two-fold less (IC50 = 81.8 +/- 12.9 microM). At concentrations of 6 to 320 microM, gnaphalin did not affect secretion of the pro-inflammatory enzymes lysozyme, myeloperoxidase and beta-glucuronidase from the neutrophil secretory granules, and did not scavenge hydrogen peroxide or hypochlorous acid. However, gnaphalin effectively scavenged superoxide radicals generated in the hypoxanthine/xanthine oxidase system (IC50 = 40 microM) and by PMA-stimulated leukocytes (> 60% at 500 microM), directly inhibited xanthine oxidase (85% at 395 microM) and inhibited Fe(3+)-ascorbate-induced liposomal peroxidation (IC50 = 215 microM). Thus, like some other flavonoids found in medicinal herbs, gnaphalin possesses an array of potentially beneficial anti-eicosanoid and free-radical scavenging properties which may alongside other constituents contribute to the claimed medicinal properties of the plant from which it is derived.
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PMID:Inhibition of leukocyte eicosanoid generation and radical scavenging activity by gnaphalin, a lipophilic flavonol isolated from Helichrysum picardii. 1048 68

1,3-beta-D-glucans (glucans) are structural elements in the cell walls of yeast and fungi with immunomodulatory properties, mediated through their ability to activate macrophages. This study assessed the activation of cells of the peritoneal cavity between 3 and 90 days after i.p. injection of particulate yeast glucan differing in molecular weight (MW) and degree of (1,6)-linkages. Female QS mice, 7-9 weeks of age, were injected, i.p., with varying doses of low (< 5 x 10(5)), medium (1-2 x 10(6)) or high (> 3 x 10(6)) MW glucans, all with low (< 5%) beta-(1,6)-linkages, or high MW (> 3 x 10(6)) glucan with high 1,6-linkages (> 20%). All glucans induced a transient increase in the proportion of neutrophils and eosinophils and a reduction in mast cell numbers in the peritoneal cavity. Peritoneal macrophages showed an altered morphology, increased intracellular acid phosphatase, increased LPS-stimulated NO production and increased PMA-stimulated superoxide production. There were no significant changes in serum lysozyme levels. Most macrophage activities returned to control levels by 28 days post injection of 1, 3-beta-D-glucan. There was a trend for higher MW or (1,6)-linked, (1, 3)-beta-D-glucans to be more stimulatory. It was concluded that particulate yeast (1,3)-beta-D-glucan is an effective stimulator of immune function, the efficiency of which may be influenced by the MW and degree of (1,6)-linkages.
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PMID:The effect of molecular weight and beta-1,6-linkages on priming of macrophage function in mice by (1,3)-beta-D-glucan. 1054 Feb 5

We evaluated the relationship between apical surface fluid (ASF) and protein secretion in Calu-3 cells grown at an air-liquid interface. Calu-3 monolayers responded to forskolin, a cystic fibrosis transmembrane regulator (CFTR) channel agonist, by secreting a significant amount of ASF. Such a response from Calu-3 monolayers was not observed with CFTR channel blockers glybenclamide and DPC. Other ion channel mediators, PGF-2alpha, PMA, DNDS, and DIDS, had no effect on Calu-3 ASF secretion. Forskolin decreased Calu-3 protein secretion and glybenclamide increased protein secretion. Similarly, forskolin decreased Calu-3 lysozyme secretion, whereas glybenclamide and DPC increased lysozyme secretion. We observed significant changes in Calu-3 fluid and protein secretions with ion channel mediators known to alter CFTR activity. Our results demonstrate a functional link between fluid and protein secretions in Calu-3 apical surface and suggested a possible involvement of CFTR in these processes.
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PMID:Regulation of apical surface fluid and protein secretion in human airway epithelial cell line Calu-3. 1519 85

Previous studies have identified swine helper memory T cells as CD4+CD8alpha+SLADR+. We have recently described a new porcine surface antigen (2E3) selectively expressed on CD4+ T cells that allows to divide these cells into naive (2E3+) and effector/memory (2E3-). However, although the majority of CD4+2E3- cells are CD8alpha+SLADR+, a minor proportion do not express SLADR and/or CD8alpha. Here, we have analyzed the functional capacity of these CD4+2E3- subsets to proliferate to a recall antigen. Both SLADR- and CD8alpha- cells proliferated in response to lysozyme, but at lower levels compared to the whole population CD4+2E3-. Besides, after activation with PMA plus ionomycin, CD4+2E3-SLADR- T cells produced IFNgamma and TNFalpha, although they did also in lower proportion than the whole CD4+2E3- population. Most of the IFNgamma-TNFalpha+, IFNgamma+TNFalpha+, IFNgamma+TNFalpha- cells were CD8alpha+ and CD45RA-, while IFNgamma-TNFalpha- cells showed a less differentiate phenotype.
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PMID:Analysis of functional heterogeneity of porcine memory CD4+ T cells. 1570 68

The regulation of neutrophil functions by Type I cGMP-dependent protein kinase (cGKI) was investigated in wild-type (WT) and cGKI-deficient (cGKI-/-) mice. We demonstrate that murine neutrophils expressed cGKIalpha. Similar to the regulation of Ca2+ by cGKI in other cells, there was a cGMP-dependent decrease in Ca2+ transients in response to C5a in WT, but not cGKI-/- bone marrow neutrophils. In vitro chemotaxis of bone marrow neutrophils to C5a or IL-8 was significantly greater in cGKI-/- than in WT. Enhanced chemotaxis was also observed with cGKI-/- peritoneal exudate neutrophils (PE-N). In vivo chemotaxis with an arachidonic acid-induced inflammatory ear model revealed an increase in both ear weight and myeloperoxidase (MPO) activity in ear punches of cGKI-/- vs WT mice. These changes were attributable to enhanced vascular permeability and increased neutrophil infiltration. The total extractable content of MPO, but not lysozyme, was significantly greater in cGKI-/- than in WT PE-N. Furthermore, the percentage of MPO released in response to fMLP from cGKI-/- (69%) was greater than that from WT PE-N (36%). PMA failed to induce MPO release from PE-N of either genotype. In contrast, fMLP and PMA released equivalent amounts of lysozyme from PE-N. However, the percentage released was less in cGKI-/- (approximately 60%) than in WT (approximately 90%) PE-N. Superoxide release (maximum velocity) revealed no genotype differences in responses to PMA or fMLP stimulation. In summary, these results show that cGKIalpha down-regulates Ca2+ transients and chemotaxis in murine neutrophils. The regulatory influences of cGKIalpha on the secretagogue responses are complex, depending on the granule subtype.
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PMID:Neutrophil dysfunction in guanosine 3',5'-cyclic monophosphate-dependent protein kinase I-deficient mice. 1603 36

Two approaches have been used to isolate and identify proteins of the granules of neutrophils of the tammar wallaby, Macropus eugenii. Stimulation with PMA, Ionomycin and calcium resulted in exocytosis of neutrophil granules as demonstrated with electron microscopy. However proteomic analysis using two dimensional gel electrophoresis, in-gel trypsin digestion followed by nano liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) failed to identify any anticipated granule proteins in the reaction supernatants. Subsequent use of differential centrifugation and lysis followed by the application of the same proteomic analysis approach resulted in the isolation and confident identification of 39 proteins, many of which are known to be present in the granules of neutrophils of eutherian mammals or play a role in degranulation. These proteins notably consisted of the known antimicrobials, myeloperoxidase (MPO), serine proteinase, dermcidin, lysozyme and alkaline phosphatase. A number of important known antimicrobials, however, were not detected and these include defensins and cathelicidins. This is the first report of the neutrophil granule proteins of any marsupial and complements previous reports on the cytosolic proteins.
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PMID:In search of neutrophil granule proteins of the tammar wallaby (Macropus eugenii). 1770 83

Strong chiral discrimination and site-selective photocleavage of two model proteins, lysozyme and bovine serum albumin (BSA), by new pyrenyl probes are reported here. The enantiomeric pyrenyl probes D-phenylalanine-1(1-pyrene)methylamide (PMA- D-Phe) and L-phenylalanine-1(1-pyrene)methylamide (PMA- l-Phe) were synthesized by coupling the carboxyl function of D-phenylalanine or L-phenylalanine with the amino group of 1(1-pyrene)methylamine. Binding affinities of the two enantiomers with the proteins were quantitated in absorption titrations. BSA indicated 10-fold selectivity for PMA- D-Phe, and the binding constants for the L- and D-enantiomers were 3.8 x 10(5) and 4.0 x 10(6) M(-1), respectively. Lysozyme, similarly, indicated a 6-fold preference for PMA- D-Phe with binding constants of 3.3 x 10 (5) and 2.0 x 10(6) M(-1) for the L- and D-isomers, respectively. Such strong chiral discrimination illustrates the key role of the chiral center of the probe (Phe) in the binding interactions. The enantiomers were tested to examine how the chiral discrimination for their binding influences reactivity toward protein photocleavage. Irradiation of the probe-protein complexes, at 342 nm in the presence of hexammine cobalt(III) chloride, resulted in the cleavage of the protein backbone. Photocleavage did not proceed in the dark or in the absence of the pyrenyl probes. Both enantiomers indicated low reactivity with BSA (<5% yield), while large photocleavage yields ( approximately 57%) have been noted with lysozyme. This lysozyme photocleavage yield is a significant improvement over previous reports. However, both enantiomers cleaved lysozyme at the same location between Trp108-Val109, despite the strong chiral selectivity for binding. H-atom abstraction from Trp 108, accessible from the active site cleft, could initiate the observed peptide bond cleavage.
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PMID:Chiral protein scissors activated by light: recognition and protein photocleavage by a new pyrenyl probe. 1859 76


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