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)

Cocaine and its derivatives blunted responses of neutrophils (cell/cell aggregation, up-regulation of the receptor for C3bi (CR3, CD11b/CD18), generation of superoxide anion (O2-) and degranulation to various stimuli. The order of potency of these agents was the same as that for local anesthesia: tetracaine greater than bupivacaine greater than cocaine greater than lidocaine. Neutrophil aggregation elicited by the chemoattractant FMLP (10(-7) M) was inhibited by cocaine (10 mM) to 13.6 +/- 6% of control (p less than 0.002); the IC50 was approximately 4 mM. Cocaine and the other local anesthetics not only inhibited the upregulation of CR3 and O2- generation, but also blocked degranulation of cytochalasin B-treated cells. Cocaine (10 mM) reduced beta-glucuronidase and lysozyme secretion to 4.3 +/- 0.7 and 13 +/- 2.2% controls, respectively; its IC50 was 4 mM. Local anesthetics added after ligand/receptor engagement (FMLP) interrupted aggregation and halted generation of O2-. Moreover, local anesthetics rapidly inhibited aggregation, O2- generation, and degranulation elicited by PMA (1 microgram/ml) or the Ca ionophore A23187 (10 microM): the effects of cocaine could therefore not be attributed to unique actions at the FMLP receptor. Peak levels of intracellular Ca2+ ([Ca]i) at 5 to 10 s, and levels of [Ca]i 120 s after FMLP in Fura 2-loaded cells were significantly lower in cells treated with lidocaine, findings that could be explained by enhanced 45Ca2+ efflux from neutrophils. In cells loaded with bis(carboxyethyl)carboxyfluorescine (pH indicator) local anesthetics failed to affect the initial FMLP-induced (0 to 15 s) drop of pHi but inhibited the later (120 s) realkalinization of the cytosol (lidocaine, bupivacaine). Most remarkably, autoradiographs of SDS gels prepared from stimulated, 32P-labeled neutrophils treated with local anesthetics showed no difference from resting cells, either with respect to patterns of phosphorylation and dephosphorylation or their kinetics. Labeling of a 47-kDa protein, a component of the reduced nicotinamide-adenine dinucleotide phosphate-oxidase system, was unchanged. The effects of local anesthetics, which blunt neutrophil responses without affecting protein phosphorylation, suggest that protein phosphorylation is an insufficient signal for neutrophil activation. Inasmuch as cocaine and its derivatives affect cell functions at sites distal to activation of protein kinase C, these agents should prove useful in uncoupling protein phosphorylation from functional responses.
 ...
PMID:Cocaine and its derivatives blunt neutrophil functions without influencing phosphorylation of a 47-kilodalton component of the reduced nicotinamide-adenine dinucleotide phosphate oxidase. 216 79

The effects of pertussis toxin (PT) on human neutrophil responses mediated by the 42-kDa IgG Fc R (Fc gamma R42) were compared with its effects on responses mediated by the FMLP receptor. Pre-treatment of neutrophils with PT completely inhibited FMLP stimulation of superoxide production and blocked over 95% of FMLP-stimulated degranulation. PT inhibited superoxide production stimulated by Fc gamma R42 cross-linking by 92%. In contrast, degranulation stimulated by Fc gamma R42 was only partially inhibited, with beta-glucuronidase release inhibited by 54%, lysozyme by 33%, and lactoferrin by 78%. With either stimulus, PT inhibition was maximal in the range from 1.8 to 2 micrograms/ml. Responses to both stimuli declined in a parallel fashion with increasing time of exposure to PT with maximal inhibition occurring after 2 h of exposure. Inhibition of FMLP responses and Fc gamma R42-mediated superoxide production, but not degranulation, correlated with ADP-ribosylation of a 45-kDa membrane protein. Inhibition by PT of Fc gamma R42-mediated responses was not due to a change in receptor number. These data suggest that activation of polymorphonuclear neutrophils via Fc gamma R42 proceeds through two pathways, only one of which is regulated by a PT-sensitive G protein.
 ...
PMID:Pertussis toxin inhibits human neutrophil responses mediated by the 42-kilodalton IgG Fc receptor. 296 66

The working hypothesis of many studies of shock has been that naloxone acts by blocking centrally and/or peripherally located opioid receptors. At plasma concentrations used to treat experimental shock (10(-6) M and above), naloxone inhibited the in vitro release of superoxide (O2-) by human neutrophils that were stimulated by the E. coli peptide N-formyl methionyl leucyl phenylalanine (FMLP). Superoxide release stimulated by phorbol 12,13-dibutyrate (PDB) was also inhibited by naloxone. Naloxone had no effect on the FMLP-stimulated release of beta-glucuronidase or lysozyme. Naloxone had no effect on 3H FMLP receptor binding. Studies utilizing 3H naloxone revealed the presence of a ligand-specific naloxone binding site on human neutrophils with a Kd of 1.2 X 10(-5) M, which is close to the ID50 of the inhibitory effect upon O2- release (1.8 X 10(-5). Thyrotropin releasing factor (TRF) had no effect upon 3H naloxone binding or on O2- release. Verapamil, a calcium channel blocker, inhibited 3H naloxone binding, and O2- release while nifedipine, another calcium channel blocker had no effect on either assay except at 10(-4) M, at which concentration 3H naloxone binding as well as the release of O2- were increased. These experiments suggest that the inhibitory effect of naloxone upon O2- release is mediated via a specific binding site.
 ...
PMID:Inhibition by naloxone of neutrophil superoxide release: a potentially useful antiinflammatory effect. 302 81

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.
 ...
PMID:Chemoattractant receptor functions in human polymorphonuclear leukocytes are divergently altered by membrane fluidizers. 631 May 54

Binding of chemoattractant to polymorphonuclear leukocytes (PMNL) triggers a series of events like polymerization of actin and tubulin, orientation of cells, chemotaxis, increase in fluid pinocytosis and phagocytosis, and stimulation of microbicidal pathways which includes lysosomal degranulation and generation of reactive oxygen species. Earlier studies from our laboratory have shown that stimulation of chemotaxis, fluid pinocytosis, and actin polymerization of CML PMNL in response to a synthetic chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP) is significantly lower than that in normal PMNL. It is not known whether this lower response of CML PMNL to fMLP is a global phenomenon involving different chemoattractant receptors or is restricted to the fMLP pathway. We have evaluated chemoattractant induced degranulation process in normal and CML PMNL to fMLP, platelet activating factor (PAF), leukotriene B4 (LTB4), and an analogue of fMLP viz formyl-methionine-1 aminocyclooctane 1 carboxylic acid-phenylalanine-O-methionine (FACC8) using release of lysozyme as a parameter. We find that after stimulation with fMLP and FACC8, the mean percent release of lysozyme was significantly lower in CML PMNL as compared to that in normal cells (P < 0.001). There was no significant difference between the two after stimulation with PAF and LTB4. The results indicate that the fMLP pathway is suppressed in CML granulocytes whereas PAF and LTB4 pathways appear unaltered in these cells. We therefore also studied the kinetics of peptide-receptor interaction with a labelled hexapeptide fNLPNTL which binds to the fMLP receptor. Our results show that the number of fMLP receptors/cell is significantly lower in CML PMNL (P < 0.05) than in normal PMNL, while their affinity constants and dissociation constants were comparable.
 ...
PMID:Granulocytes from chronic myeloid leukemia (CML) patients show differential response to different chemoattractants. 875 80