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)

Exposure of human neutrophils to 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (leukotriene B4, LTB4) resulted in a time- and concentration- (10(-9)-10(-6) M) dependent extracellular release of granule-associated lysozyme and myeloperoxidase (MPO). Enzyme extrusion was negligible if cells were not pretreated with cytochalasin B prior to exposure to LTB4. A time-dependent deactivation of granule exocytosis was observed in neutrophils which were stimulated with LTB4 prior to contact with cytochalasin B. LTB4-induced enzyme release was markedly enhanced in the presence of extracellular calcium. Nevertheless, significant enzyme discharge occurred in the absence of extracellular calcium, and the percent of total activity released was not altered in the presence of EGTA. The calmodulin antagonist, trifluoperazine (TFP), and the intracellular calcium antagonist, 8-(N,N-diethylamino)-octyl-(3,4,5-trimethoxy)benzoate hydrochloride (TMB-8), caused a dose-related inhibition of enzyme release from LTB4-stimulated neutrophils. Degranulation was suppressed by the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), and the sulfhydryl reagents iodoacetic acid (IA) and N-ethylmaleimide (NEM). Sodium cyanide was inactive. Two inhibitors of transmethylation, 3-deazaadenosine (3-DZA) and L-homocysteine thiolactone (HCTL), alone or in combination, had no effect on LTB4-elicited degranulation. The protein synthesis inhibitor, cycloheximide, was inactive. Neutrophils pretreated with LTB4 or 5(S),12(R),20-trihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (20-OH-LTB4, an omega-oxidation metabolite of LTB4) were desensitized to the subsequent exposure to LTB4. Cross-desensitization was also demonstrated between LTB4 and 20-OH-LTB4. The stimulus specific nature of LTB4-induced desensitization of neutrophil degranulation was demonstrated by the fact that cells exposed to 1-O-hexadecyl/octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC) or N-formyl-methionyl-leucyl-phenylalanine (FMLP) were capable of inducing granule exocytosis from LTB4-pretreated neutrophils. Enzyme release from LTB4-treated cells was suppressed with the phospholipase inhibitor, 4-bromophenacyl bromide (4-BPB), the cyclooxygenase/lipoxygenase inhibitor, ETYA, and the 5-lipoxygenase inhibitor, U-60, 257. However, the cyclooxygenase inhibitor, flurbiprofen, exerted a weak suppressive effect on LTB4-induced degranulation.
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PMID:Activation of the human neutrophil secretory process with 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid. 609 46

Pepstatin A, a chemotactic pentapeptide, elicited a concentration-dependent extracellular release of granule-associated beta-glucuronidase and lysozyme from, and generation of superoxide anion (O2-) by, cytochalasin B (CB)-treated human neutrophils. Prior exposure of neutrophils to pepstatin A before the addition of CB, suppressed, in a time-dependent fashion, the subsequent production of O2- and exocytotic response. The rate and amount of enzymes released and O2- generated by pepstatin A-activated neutrophils were significantly enhanced in the presence of extracellular calcium. Pepstatin A-elicited degranulation and O2- production were suppressed by the intracellular calcium antagonist, 8-(N,N-diethylamino)-octyl-(3, 4, 5-trimethoxy) benzoate hydrochloride (TMB-8). Granule exocytosis and O2- generation by pepstatin A-treated neutrophils were suppressed by the sulphydryl reagents, N-ethylmaleimide (NEM) and iodoacetic acid (IA), and by the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG). Sodium cyanide was inactive. Preincubation of neutrophils with pepstatin A "desensitized' the cells to a subsequent exposure to pepstatin A or the chemotactic tripeptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP). Pepstatin A-induced desensitization of granule enzyme release and O2- generation appears to be stimulus-specific in that phorbol myristate acetate (PMA) was capable of eliciting normal responses from pepstatin A-pretreated cells. The morphological changes observed in pepstatin A-treated neutrophils are reminiscent of those seen in cells exposed to FMLP.
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PMID:Biochemical, metabolic and morphological characteristics of human neutrophil activation with pepstatin A. 630 51

1-O-Hexadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (C16-AGEPC) and 1-O-octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (C18-AGEPC) stimulated a time- and concentration-dependent release of granule-associated lysozyme and beta-glucuronidase from human neutrophils. Maximum discharge of granule enzymes occurred between 30 and 60 sec after neutrophil exposure to C16- or C18-AGEPC (0.01-10 microM). Less than 10% of total enzyme activity is released when cells are not preincubated with cytochalasin B prior to interaction with the AGEPC analogs. A time-dependent desensitization for granule exocytosis was observed in neutrophils which were stimulated with C18-AGEPC prior to contact with cytochalasin B. The rate and amount of enzyme released by C16- and C18-AGEPC activated neutrophils was significantly enhanced in the presence of extracellular calcium. Trifluoperazine, an inhibitor of calmodulin, caused a dose-related suppression of C18-AGEPC-induced degranulation. Granule enzyme extrusion from C18-AGEPC-treated neutrophils was inhibited by the sulfhydryl reagents, N-ethylmaleimide and iodoacetic acid, and by the glycolytic inhibitor, 2-deoxy-D-glucose. Sodium cyanide was inactive. Pretreatment of neutrophils with C16- or C18-AGEPC rendered the cells unresponsive to subsequent exposure to either AGEPC analog. C18-AGEPC-induced desensitization of neutrophil degranulation appears to be stimulus specific in that serum-treated zymosan and N-formyl-methionyl-leucyl-phenylalanine were capable of eliciting granule enzyme release from C18-AGEPC-pretreated cells.
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PMID:Characteristics of 1-O-hexadecyl- and 1-O-octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine-stimulated granule enzyme release from human neutrophils. 687 58