Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02259 (NaI)
 1,823 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antimicrobial oxidative system (myeloperoxidase (MPO), H2O2 and a halide) produced by stimulated PMNLs is simulated in vitro using horseradish peroxidase (HRP), H2O2 and NaI. Ascorbate, thiamine, levamisole and cysteine prevent and reverse the PMNL motility inhibiting effects of the HRP/H2O2/NaI system. The ability of these agents to protect the PMNL specifically from the known iodinating and oxidising abilities of this system was investigated. All four agents protect the PMNL from iodination by HRP/H2O2/NaI. However, only ascorbate and thiamine are able to reverse this process after it has occurred. Thiamine is seen on thin layer chromatography followed by autoradiography to be iodinated by this system. Ascorbate, thiamine and cysteine are able to protect the neutrophil sulfhydryl groups from oxidation by the system. One can therefore conclude that ascorbate and cysteine protect neutrophil motility from inhibition by the HRP/H2O2/NaI system by acting as reducing agents which maintain the neutrophil sulfhydryl groups. Thiamine also acts as a reducing agent, though not as effectively as ascorbate or cysteine. In addition, thiamine protects the PMNL from iodination by a competitive mechanism. The mechanism of levamisole protection is less clear but may involve scavenging of free radicals generated by the HRP/H2O2/NaI system. Protease enzymes, glycolysis and adherence are found not to be target sites for the PMNL motility inhibiting effects of the HRP/H2O2/NaI system. Further, increasing concentrations of the synthetic leukoattractant FMLP were shown to increase the auto-iodination of PMNLs without addition of extraneous peroxidase or peroxide. This data was compared with optimal FMLP concentrations for chemotaxis.
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PMID:Oxidative inhibition of polymorphonuclear leukocyte motility mediated by the peroxidase/H2O2/halide system: studies on the reversible nature of the inhibition and mechanism of protection of migratory responsiveness by ascorbate, levamisole, thiamine and cysteine. 665 35

Cefdinir, a new oral 2-amino-5-thiazolyl cephalosporin, inhibited the luminol-amplified chemiluminescence (LACL) response of human neutrophils stimulated by PMA but not opsonized zymosan, in a concentration-dependent but not time-dependent manner. The LACL response to opsonized zymosan in cytochalasin B-treated neutrophils was, however, inhibited by cefdinir. Various cephalosporins, regardless of the presence of a 2-amino-5-thiazolyl moiety, did not significantly alter the neutrophil LACL response triggered by PMA and zymosan. The LACL response induced by the calcium ionophore A23187 and FMLP was also impaired by cefdinir, and this impairment was increased in cytochalasin B-treated neutrophils. Superoxide anion generation by neutrophils, measured in terms of lucigenin-amplified chemiluminescence and cytochrome c reduction, was not altered. Spontaneous and FMLP-induced neutrophil degranulation, assessed by lysozyme and beta-glucuronidase release, were not modified by cefdinir. Furthermore, cefdinir inhibited LACL generation in cell-free systems consisting of H2O2, NaI, and either horseradish peroxidase or a myeloperoxidase-containing neutrophil extract. Orthodianisidine oxidation in these two acellular systems was inhibited by cefdinir. Cefdinir did not alter neutrophil bacterial killing at concentrations that inhibited myeloperoxidase-containing neutrophil extract-dependent reactions induced by soluble stimuli. Taken together, these data strongly suggest that cefdinir directly inhibits the activity of myeloperoxidase-containing neutrophil extract released into the extracellular medium during neutrophil stimulation by soluble mediators, but has no effect on that released into the phagolysosome during phagocytosis. This unusual property of a member of the beta-lactam family could be of interest in modulating the exaggerated inflammatory process often associated with infectious diseases.
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PMID:Cefdinir (CI-983), a new oral amino-2-thiazolyl cephalosporin, inhibits human neutrophil myeloperoxidase in the extracellular medium but not the phagolysosome. 813 56