Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ketorolac tromethamine, a new nonsteroidal anti-inflammatory agent of the pyrrolo-pyrrole group, was assayed for inhibitory effects on polymorphonuclear leukocytes (PMN) in a variety of systems. Ketorolac inhibited PMN superoxide anion generation, lysozyme release, myeloperoxidase release, adherence to plastic surfaces, and chemotaxis in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) in a dose-dependent manner. Ketorolac also inhibited phorbol myristate acetate-stimulated adherence of PMN to bovine pulmonary artery endothelial cells. The drug inhibited lysozyme and myeloperoxidase release by PMN in response to C5a but failed to inhibit C5a stimulation of PMN in any of the other assays. Levels of ketorolac required to inhibit PMN function in most systems were in the range of 0.2 to 1.0 mg/ml, but chemotaxis to fMLP was inhibited by concentrations of ketorolac as low as 1 microgram/ml. Ketorolac, currently the only nonsteroidal anti-inflammatory drug available in a parenteral form may have therapeutic usefulness in a variety of conditions thought to be mediated in part by PMN, including sepsis.
 ...
PMID:Inhibition of some human neutrophil functions by the cyclooxygenase inhibitor ketorolac tromethamine. 131 50

Recombinant human tumor necrosis factor-alpha (rTNF) stimulated increased generation of superoxide anion (O2-) by human neutrophils in a concentration-dependent fashion. Preincubation of human neutrophils with rTNF (2.2-2200 units/ml) for 10 min enhanced the subsequent generation of O2- in response to C5a and f-Met-Leu-Phe (FMLP). Recombinant TNF did not enhance O2- generation by neutrophils stimulated with phorbol myristate acetate (PMA). Recombinant TNF alone failed to induce release of myeloperoxidase (MPO) and lysozyme by neutrophils. However, it did enhance the release of MPO and lysozyme by neutrophils stimulated with C5a and FMLP, but not with PMA. Although rTNF alone (0.001-50,000 units/ml) was not chemotactic for neutrophils, preincubation of neutrophils with rTNF (0.001-0.1 units/ml) enhanced the chemotactic activity of suboptimal concentrations of C5a (0.1 nM) and FMLP (5 nM). Neutrophils treated with high concentrations of rTNF (100-10,000 units/ml) showed inhibition of random movement and of chemotaxis induced by C5a or FMLP. We conclude from these studies that rTNF primes neutrophils for enhanced responses to subsequent stimuli and thus may augment the inflammatory response by increased oxidant production and lysosomal enzyme release and promote down-regulation of chemotactic movement.
 ...
PMID:Priming of human neutrophil functions by tumor necrosis factor: enhancement of superoxide anion generation, degranulation, and chemotaxis to chemoattractants C5a and F-Met-Leu-Phe. 132 30

Previous studies indicate that oxygen radical production by 1-min activation of N-formyl-methionyl-leucyl-phenylalanine-induced chemiluminescence (CL) by whole blood is increased in subjects with previous Yersinia arthritis (YA). This finding is confirmed in the present study and extended further by demonstrating that subjects with previous YA show increased oxygen radical generation and enhanced release of myeloperoxidase from neutrophils and increased CL activity by serum, all factors that can contribute to an increase in the initial activation of CL. Initial activation was not increased in subjects who had had Yersinia enteritis without arthritis; however, intracellular oxygen radical production by purified neutrophils was significantly increased, suggesting that the cells had been primed in vivo. The water-soluble antioxidants of plasma samples tested by a peroxyl radical-trapping assay were much the same in subjects with previous YA, in subjects with previous Yersinia enteritis without arthritis, and in healthy subjects. The results suggest that aberrations in neutrophil oxygen radical production play a role in the pathogenesis of YA.
 ...
PMID:Oxygen radical production and trapping in subjects with previous Yersinia infection. 132 31

When stimulated with different stimuli, neutrophils generate various active oxygen species. These active oxygen molecules can be analyzed by luminol chemiluminescence (LCL). Phosphatidylserine (PS)-liposomes increased the formylmethionyl-leucyl-phenylalanine-induced LCL of guinea pig peritoneal neutrophils without affecting their oxygen consumption and superoxide (O2.-) generation. Similar effects of PS-liposomes were also observed in LCL of neutrophils stimulated by phorbol myristate acetate or arachidonic acid but not by opsonized zymosan. Kinetic analysis revealed that the PS-liposome-induced increase in LCL depended on extracellulary generated O2.-. Moreover, the stimulatory effect of PS could be seen only when it formed liposomal membranes. The effect of PS-liposomes was also inhibited by superoxide dismutase, catalase, and deferoxamine, an iron chelator, but not by azide, an inhibitor of myeloperoxidase. Similar enhancement of stimulation-dependent LCL response was also observed with Fe3+ and ADP-Fe3+, but the degree of enhancement was much greater with PS-liposomes than with iron and its complex. The increase in hydroxyl radical generation by PS-liposome-treated neutrophils was confirmed by experiments with EPR spectrometry using spin-trapping agents. These results suggested that the interaction of neutrophils with PS-containing membrane surface might generate reactive oxygen species that enhance the stimulus-dependent LCL response of neutrophils.
 ...
PMID:Stimulus-specific enhancement of luminol chemiluminescence in neutrophils by phosphatidylserine liposomes. 132 54

The Pseudomonas aeruginosa-derived phenazine pigments pyocyanin and 1-hydroxyphenazine (1-hp) prime human neutrophils for enhanced, stimulus-activated release of superoxide and myeloperoxidase (MPO), respectively. In the present study, the modulatory potentials of the antimicrobial agents clindamycin, erythromycin, and roxithromycin (10 and 20 micrograms/ml) on the prooxidative interactions of pyocyanin and 1-hp (12.5 microM) with human neutrophils have been investigated. Clindamycin, erythromycin, and especially roxithromycin caused dose-related inhibition of the generation of superoxide by both untreated and pyocyanin-treated neutrophils during activation with either the synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) or the calcium ionophore A23187. The antimicrobial agents also inhibited the generation of reactive oxidants by the MPO-H2O2-halide system during activation of both untreated and 1-hp-treated neutrophils by FMLP. These effects appeared to be due to drug-related interference with membrane-associated oxidative metabolism, since none of the antimicrobial agents inhibited the release of MPO by activated neutrophils, nor did they possess oxidant-scavenging properties. These data demonstrate that clindamycin, erythromycin, and especially roxithromycin antagonize the proinflammatory interactions of pyocyanin and 1-hp with neutrophils and indicate a possible therapeutic role for these antimicrobial agents in the prevention of tissue damage in diseases characterized by P. aeruginosa infection.
 ...
PMID:Clindamycin, erythromycin, and roxithromycin inhibit the proinflammatory interactions of Pseudomonas aeruginosa pigments with human neutrophils in vitro. 132 16

Activation of human neutrophils by PMA causes a post-translational incorporation of 14C-labeled tyrosine into multiple neutrophil (PMN) proteins, that is distinctly different from the enzymatic tyrosinolation of tubulin in FMLP-stimulated PMN. Post-translational incorporation of other radiolabeled amino acids, including the structurally similar amino acid phenylalanine, does not occur under identical conditions of neutrophil activation, suggesting an involvement of the phenolic hydroxyl group of tyrosine in the PMA-mediated reaction. Similar to the stimulation of PMN tubulin tyrosinolation by FMLP, the PMA-induced incorporation of tyrosine into multiple PMN proteins is closely associated with activation of the NADPH oxidase-mediated respiratory burst in stimulated PMN and can be inhibited by a variety of reducing agents, inhibitors of peroxidase-mediated reactions, and intracellular scavengers of oxygen radicals. Moreover, the PMA-induced post-translational incorporation of tyrosine does not occur in PMN from patients with chronic granulomatous disease and is significantly reduced (50%) in PMN of an individual with myeloperoxidase deficiency. A similar stimulus-induced incorporation of tyrosine into multiple PMN proteins is also observed in PMN exposed to various phagocytic stimuli, and the incorporated radioactivity in cells undergoing phagocytosis is substantially enriched (40- to 50-fold) in isolated PMN phagolysosomes. Consistent with this latter observation, HPLC fractionation of stimulated PMN proteins and analysis of the incorporated radioactivity reveal that the 14C label is primarily associated with PMN membrane proteins. Furthermore, this post-translational incorporation of tyrosine, like that associated with PMA stimulation, is associated with production of oxygen radicals and the generation of protein carbonyl derivatives, which are indicative of oxidative protein modifications via mixed function oxidases. Our findings indicate that tyrosine incorporation into membrane proteins of stimulated PMN is functionally relevant to the physiologic host-defense responses of human neutrophils undergoing phagocytosis.
 ...
PMID:A novel post-translational incorporation of tyrosine into multiple proteins in activated human neutrophils. Correlation with phagocytosis and activation of the NADPH oxidase-mediated respiratory burst. 133 Dec 34

The oxidation of free coelenterazine by superoxide anion was analyzed and compared to the oxidation by the semisynthetic photoprotein obelin, prepared by incorporation of synthetic coelenterazine into apoobelin. The oxidation of bound coelenterazine was triggered upon binding of calcium to the reconstituted photoprotein. The oxidation of free synthetic coelenterazine, in the absence of the apoprotein, was triggered by superoxide anion. The production of reactive oxygen metabolites by fMet-Leu-Phe- and 4b-phorbol 12b-myristate 13a-acetate-stimulated neutrophils was studied by means of the luminescence of synthetic coelenterazine. The features of this chemiluminescent probe were compared with those of luminol and are summarized as follows: (a) coelenterazine-dependent chemiluminescence was inhibited by superoxide dismutase; (b) coelenterazine was as sensitive as luminol in detecting the oxidative burst of neutrophils; (c) azide failed to inhibit coelenterazine chemiluminescence; (d) in contrast with luminol, which requires the catalytic removal of hydrogen peroxide, coelenterazine chemiluminescence did not depend on the activity of cell-derived myeloperoxidase. These results indicate the usefulness of coelenterazine as a very sensitive and specific chemiluminescence probe of superoxide anion.
 ...
PMID:Coelenterazine is a superoxide anion-sensitive chemiluminescent probe: its usefulness in the assay of respiratory burst in neutrophils. 133 45

We observed that the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L- phenylalanine (FMLP) induced pulmonary edema when polymorphonuclear leukocytes (PMNs) were added to isolated constant-flow buffer-perfused rabbit lungs. This study was designed to test the hypothesis that PMNs activated by FMLP induced lung injury by the modulation of reactive oxygen species (ROS), cyclooxygenase products, or cysteinyl leukotrienes (LTs). Addition of FMLP alone did not increase microvascular permeability (Kf). When PMNs were added to the isolated lung, FMLP caused an 80% increase in Kf. Wet-to-dry weight ratio was also significantly increased with PMNs + FMLP compared with FMLP only. There was a significant positive correlation between total myeloperoxidase activity in lung tissue and Kf values after FMLP (30 min). Pretreatment with two dissimilar cyclooxygenase inhibitors, meclofenamate or ibuprofen, had no effect on the PMN + FMLP-induced increase in Kf. However, the ROS inhibitor catalase and the nonantioxidant LT synthesis blocker MK 886 inhibited the PMN + FMLP increase in Kf. Perfusate levels of LTs (LTC4, -D4, and -E4) were significantly increased from baseline values 30 min after FMLP. Both MK 886 and catalase suppressed the elevation of LTs after PMN + FMLP. These results indicate that FMLP increased a pulmonary microvascular permeability in isolated buffer-perfused rabbit lungs that is PMN dependent and mediated by LT produced possibly by a result of ROS production.
 ...
PMID:Mechanisms of increased pulmonary microvascular permeability induced by FMLP in isolated rabbit lungs. 133 54

In addition to their increased potency as H1 blockers and their nonsedating effects, the second-generation antihistamines have other unusual and potentially beneficial properties. Evidence is accumulating from several laboratories that at least one of these agents under investigation, cetirizine, may be effective in inhibiting the late reaction. The Johns Hopkins group showed that during the cutaneous late phase response (LPR), histamine release was not altered by cetirizine, 20 mg, pretreatment. The most dramatic effect of cetirizine was attenuation of inflammatory cell migration into the chamber. Eosinophils, neutrophils, and basophils were reduced by about 75% during hours 6 to 8. It can be concluded that cetirizine influences the LPR by causing a reduction in the inflammatory cell infiltrate. Cetirizine, 10 mg, orally once a day also induced a significant decrease in the wheal and flare skin reactions caused by pollen, histamine, and compound 48/80. Cetirizine inhibited eosinophil recruitment and platelet-activating factor (PAF) in skin chambers 24 hours after pollen challenge. We and others have studied the mechanisms of this effect. The release of eosinophil peroxidase induced by PAF and formyl-methionyleucyl/phenylalanine was not attenuated by cetirizine. At therapeutic concentrations, however, cetirizine has a potent inhibitory action in vitro on eosinophil chemotaxis induced either by formyl-methionyleucyl/phenylalanine or PAF and also on IgE-dependent stimulation of platelets. In a separate study in patients with chronic urticaria, cetirizine markedly reduced both the immediate wheal and flare induced by PAF and the delayed reaction at six hours. These results suggest that cetirizine acts on eosinophil migration to inhibit the late reaction.
 ...
PMID:Use of cetirizine to investigate non-H1 effects of second-generation antihistamines. 134 37

Anti-neutrophil cytoplasm antibodies (ANCA) are markers of systemic vasculitis for which a pathogenetic role has been postulated. We have examined the effect of these autoantibodies on the function of normal human neutrophils in vitro. In the presence of ANCA positive sera luminol-amplified chemiluminescence was significantly increased compared to the values seen in the presence of normal or anti-double stranded DNA positive sera (P < 0.01). Five of six ANCA positive F(ab)2 preparations also produced significant neutrophil activation as demonstrated by the chemiluminescence response. This response was totally abrogated by the addition of neutrophil cytoplasm extract, containing the ANCA antigen. Addition of inhibitors to the chemiluminescence system demonstrated that the chemiluminescence response was inhibited by azide and salicylhydroxamic acid and reduced by histidine, suggesting that the chemiluminescence response was due to activation of myeloperoxidase, with generation of singlet oxygen. The chemotactic response to f-Met-Leu-Phe, a bacterial chemotactic peptide, was significantly augmented in the presence of ANCA. Chemotaxis to zymosan-activated serum and chemokinesis was not affected. Phagocytosis was also unaffected. We propose that neutrophil activation and modulation of neutrophil migration by ANCA may be of pathogenetic significance in systemic vasculitis.
 ...
PMID:Activation of normal neutrophils by anti-neutrophil cytoplasm antibodies. 142 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>