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)

We have examined the effects of very pure (greater than 99.8%) chemically synthesized leukotriene B4 of verified structure on the chemotactic and secretory behavior of human polymorphonuclear leukocytes (PMN). The synthetic material is highly chemotactic and shows the same concentration dependence of this activity as does natural LTB4. Synthetic LTB4 is also a weak degranulating agent in cytochalasin B treated PMN. Maximally it released 11%, 17% and 26% as much N-acetyl-beta-D-glucosaminidase, myeloperoxidase and lysozyme as did N-formyl-methionine-leucine-phenylalanine (fMLP). Thus LTB4 differs significantly from other chemotaxins, such as C5a and fMLP, in that it is a poor secretagogue for enzymes of the specific and azurophilic granules of human PMN.
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PMID:Synthetic leukotriene B4 is a potent chemotaxin but a weak secretagogue for human PMN. 630 18

Neutrophils respond to a variety of stimuli by generating superoxide anion, degranulating, and aggregating. Because it has been suggested that fusion of granules with the plasmalemma (degranulation) is necessary for aggregation and superoxide anion generation, we have tested whether these responses can be demonstrated in "neutrophilic cytoplasts" (granule-free vesicles of cytoplasm enclosed by plasmalemma). When examined by electron microscopy, cytoplasts were found to be approximately 4 microns in diameter and essentially granule free. Cytoplasts exposed to fMet-Leu-Phe (0.1 microM) generated superoxide anion after a lag of 16 sec but released no detectable beta-glucuronidase, lysozyme, or elastase. Aggregation of cytoplasts, as measured by changes in light transmission, was also activated by fMet-Leu-Phe; no lag period was observed. Electron microscopy of the aggregates demonstrated clusters of cytoplasts with a scalloped appearance. Superoxide anion generation and aggregation of cytoplasts were also activated by phorbol 12-myristate 13-acetate, concanavalin A, and leukotriene B4. Exposure of cytoplasts to the dye 3,3'-dihexyloxacarbocyanine iodide (DiOC6(3)] led to dye uptake and enhancement of fluorescence, implying that the vesicles were sealed and maintained a membrane potential across the plasmalemma. Exposure of DiOC6(3)-loaded cytoplasts to fMet-Leu-Phe and PMA caused a rapid loss of dye fluorescence that was not inhibited by CN-, compatible with their lack of mitochondria. Exposure of dye-loaded cytoplasts to concanavalin A or leukotriene B4 caused an increase in fluorescence--i.e., a hyperpolarization. These results demonstrate that degranulation is not a prerequisite for aggregation or superoxide anion generation. The retention of ionic gradients and changes in membrane potential, as measured by DiOC6(3) fluorescence changes, suggest a fundamental role for ionic movements in activating superoxide anion generation and aggregation.
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PMID:Granulocytes without degranulation: neutrophil function in granule-depleted cytoplasts. 630 64

The chemotactic factor receptor on leukocytes initiates several cellular responses including chemotaxis, lysosomal enzyme secretion, and O2- production. The latter two responses require approximately 10-100 times more chemoattractant than is required for chemotaxis. We determined the effects of membrane fluidizers on the binding characteristics and the functional activities of the oligopeptide fMet-Leu-Phe chemotactic factor receptor on polymorphonuclear leukocytes. Fluidization was induced by aliphatic alcohols and monitored by diphenylhexatriene fluorescence polarization. Low doses of n-butanol (0.25%) and n-pentanol (0.1%) were nontoxic to the leukocytes yet reduced their diphenylhexatriene-induced polarization, indicating increased membrane fluidity. At these doses of alcohols, the affinity of the fMet-Leu-Phe receptor was enhanced from Kd = 25.5 +/- 7.6 nM to Kd = 5.2 +/- 0.9 nM and Kd = 6.0 +/- 0.9 nM, respectively. Chemotaxis was also increased, as indicated by the decrease, by a factor of approximately 1/3 in the ED50 for fMet-Leu-Phe, as well as by a 1.5-fold increase in the maximal distance of migration in the presence of 0.25% butanol or 0.1% pentanol. In contrast to chemotaxis, the alcohols depressed fMet-Leu-Phe stimulation of O2- production by 90% although they had no effect on phorbol 12-myristate 13-acetate-induced O2- production. Secretion of lysozyme was also inhibited. Thus, the affinity of the fMet-Leu-Phe receptor can be modulated by membrane fluidizers. The higher affinity state of the receptor induced by the alcohols is more efficient in transducing chemotactic signals but is deficient in mediating O2- production or secretion. Thus, the transduction mechanisms for the various biological activities of the chemotactic factor receptor are heterogeneous and can be differentially manipulated by membrane fluidizers.
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PMID:Chemoattractant receptor functions in human polymorphonuclear leukocytes are divergently altered by membrane fluidizers. 631 May 54

Aging is assumed to decrease lysosomal enzyme release from polymorphonuclear leukocytes (PMN). A synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) was utilized to stimulate enzyme release of PMN from 45 human subjects, 21 males and 24 females, ranging in age from 22-83 yr old. Results of the studies showed no sex differences in the stimulation of enzyme release for either age group. However, stimulation was found to significantly decline in both males and females over 50 yr old compared to subjects under 50 yr old. The linear formulae for beta-glucuronidase, beta-galactosidase and lysozyme in male subjects were Y = 6.5X + 617.2, Y = -1.9X + 311.5 and Y = -1.9X + 327.3 with correlation coefficient of -0.685, -0.352 and -0.401, respectively. The linear formulae in females were Y = -5.2X + 536.6, Y = -3.0X + 340.6 and Y = -1.7X + 333.6 with correlation coefficient of -0.582, -0.303 and -0.462, respectively. These findings suggest that there was an age-related decline of response to the stimulant, fMet-Leu-Phe.
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PMID:Age-related decline in lysosomal enzyme release from polymorphonuclear leukocytes after N-formyl-methionyl-leucyl-phenylalanine stimulation. 642 Jan 76

Neutrophils and macrophages are known to undergo significant modifications in their morphology and basal metabolism in response to chemical factors, in particular changes in the shape, movement, phagocytic activity and degranulation. These phenomena often involve an increase in chemokinesis and cellular secretory activity, usually expressed in antimicrobial activity. Once activated, the cells can move quickly towards the source of the stimulus, where they produce and release great amounts of enzymes (e.g. proteases, hydrolases, lysozyme) and reactive oxygen metabolites (e.g. O2-., H2O2, OH.). This study has examined the ability of surfaces of selected biomaterials to influence neutrophil morphology and locomotion. The surface of two films derived from hyaluronic acid derivatives were compared with that of glass. The two hyaluronic acid derivatives, despite having a similar chemical structure, were shown to interact with human neutrophils in different ways. A hyaluronic acid ethyl ester stimulated the whole population of neutrophils to take up a non-spherical morphology (polarize) and to move with a velocity similar to that of N-formyl-methionine-leucine-phenylalanine-stimulated cells on a glass surface. In contrast, only 44% of the examined cells on the surface of hyaluronic acid benzyl ester were polarized and their mean speed was only slightly higher with respect to that found with non-stimulated cells on glass. Moreover, while on the benzyl ester and on glass a correlation between neutrophil circularity (i.e. the shape of the cell) and cell speed was found, the ethyl ester did not show any correlation.
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PMID:Human neutrophil chemokinesis and polarization induced by hyaluronic acid derivatives. 813 Mar 17

Eleven chalcone derivatives have been tested for their inhibitory effects on platelet aggregation in rabbit platelet suspension and the activation of mast cells and neutrophils. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the compounds and some also had a potent inhibitory effect on collagen-induced platelet aggregation and cyclooxygenase. Some hydroxychalcone derivatives showed strong inhibitory effects on the release of beta-glucuronidase and lysozyme, and on superoxide formation by rat neutrophils stimulated with the peptide fMet-Leu-Phe (fMLP). We found that the anti-inflammatory effect of 2',5'-dihydroxychalcone was greater than that of trifluoperazine. 2'5'-Dihydroxy and 2',3,4,5'-tetrahydroxyl chalcones, even at low concentration (50 microM), tested in platelet-rich plasma from man almost completely inhibited secondary aggregation induced by adrenaline. These results suggest that the anti-platelet effects of the chalcones are mainly a result of inhibition of thromboxane formation.
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PMID:2',5'-Dihydroxychalcone as a potent chemical mediator and cyclooxygenase inhibitor. 917 90


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