UMLS:C0043167 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of zinc on the production of active oxygen species were investigated in rat neutrophils by chemiluminescence and spectrophotometric assays. The luminol-dependent chemiluminescence in unstimulated neutrophils showed a single peak. Zinc at concentrations lower than 0.1 mM augmented the intensity of chemiluminescence and showed a bimodal pattern, the first peak of which was inhibited by superoxide dismutase and catalase, while the second peak disappeared in the presence of catalase, but was unaffected by superoxide dismutase. At the same concentrations of zinc, O2- and H2O2 production increased, but secretion and activity of myeloperoxidase were not affected. Zinc at 0.1 mM enhanced the second peak of luminol-dependent chemiluminescence, and concomitantly O2- and H2O2 production of neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine. Homogenized neutrophils showed a bimodal pattern on induction by zinc, the second peak of which was inhibited slightly by catalase and completely by sodium azide, but was not inhibited by superoxide dismutase. Zinc-induced O2- production was inhibited by pertussis toxin, but was not significantly inhibited by a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), or a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). These results suggest that zinc can augment luminol-dependent chemiluminescence by increasing O2- production through the classical signal transduction pathway, and by increasing H2O2 not via O2-.
...
PMID:Effects of zinc on production of active oxygen species by rat neutrophils. 775 58

Two tyrosine kinase-dependent pathways exist for activation of the respiratory burst by polymorphonuclear leukocyte (PMN) immunoglobulin G Fc receptors. Direct ligation of Fc gamma RII activates the respiratory burst, but ligation of the glycan phosphoinositol-linked Fc gamma RIIIB does not. Instead, this receptor and the integrin complement receptor CR3 synergize in activation of the respiratory burst (Zhou, M.-J., and Brown, E. J. (1994) J. Cell Biol. 125, 1407-1416). Here we show that direct ligation of Fc gamma RII leads to activation and Triton X-100 insolubility of the Src family kinase Fgr, without effect on the related myeloid Src family member Hck. In contrast, adhesion of PMN via Fc gamma RIIIB leads to activation and Triton X-100 insolubility of Hck but not Fgr. The exclusive association of Fc gamma RIIIB with Hck activation and Triton insolubility is not solely a result of its glycan phosphoinositol anchor, since decay accelerating factor (CD55), another prominent glycan phosphoinositol-anchored PMN protein, is associated with Fgr insolubility to a greater extent than Hck. Ligation of decay accelerating factor, with or without coligation of CR3, does not activate the PMN respiratory burst. Coligation of Fc gamma RIIIB with Fc gamma RII overcomes the pertussis toxin inhibition of H2O2 production in response to direct ligation of Fc gamma RII. These data support the hypothesis that activation of Hck upon Fc gamma RIIIB ligation has a role in generation of the synergistic respiratory burst.
...
PMID:Distinct tyrosine kinase activation and Triton X-100 insolubility upon Fc gamma RII or Fc gamma RIIIB ligation in human polymorphonuclear leukocytes. Implications for immune complex activation of the respiratory burst. 776 58

The production of hydrogen peroxide (H2O2) as an essential process for iodide organification is a key reaction in TSH-induced thyroid hormone synthesis. Here we characterize the signal transduction pathway involved in TSH-induced H2O2 production in FRTL-5 thyroid cells. At higher than 1 nM TSH, N6-(L-2-phenylisopropyl)adenosine (PIA), an adenosine receptor agonist having, by itself, no influence on H2O2 generation, potentiated this TSH action, whereas the TSH increase and PIA addition reduced cAMP accumulation. RO 20-1724, a phosphodiesterase inhibitor, amplified the TSH-induced cAMP accumulation, but did not change H2O2 generation in the whole range of TSH used. Ca(2+)-mobilizing agonists, GTP and ATP, also induced H2O2 production without stimulating cAMP accumulation. Chelation of intracellular Ca2+ markedly inhibited the TSH action, but intracellular Ca2+ increases by either thapsigargin or ionomycin mimicking it. All of the findings show the participation of Ca2+, but not cAMP, in the action of TSH. Desensitization of protein kinase-C (PKC) did not influence the receptor-mediated H2O2 production, suggesting the reduced importance of PKC activation compared to Ca2+ signaling to the reaction. A rise in intracellular Ca2+ independent of receptor activation also induced H2O2 production as well as arachidonate release, and both were potentiated by PIA. In addition, inhibitors of phospholipase-A2 and the arachidonate metabolic pathway depressed H2O2 generation, suggesting the participation of an arachidonate cascade in the Ca(2+)-dependent H2O2 production. Lipoxygenase inhibitors depressed the Ca2+ action without influencing arachidonate release, suggesting the involvement of a lipoxygenase product(s) of arachidonate in the Ca(2+)-signaling mechanism. In conclusion, in FRTL-5 cells, TSH-induced H2O2 production is mediated not by cAMP, but by the phospholipase-C/Ca2+ cascade, possibly followed by the Ca(2+)-dependent phospholipase-A2/arachidonate cascade. PIA amplifies TSH-induced H2O2 production at the steps of phospholipase-C and phospholipase-A2 activation in a pertussis toxin-sensitive manner.
...
PMID:Thyrotropin-induced hydrogen peroxide production in FRTL-5 thyroid cells is mediated not by adenosine 3',5'-monophosphate, but by Ca2+ signaling followed by phospholipase-A2 activation and potentiated by an adenosine derivative. 782 20

In this report we evaluate the role of catalase in the survival of Bordetella pertussis within human polymorphonuclear leukocytes (PMNs). Crude extracts of B. pertussis exhibited a single catalase activity when subjected to non-denaturing polyacrylamide gel electrophoresis and assayed for catalase activity. A plasmid containing B. pertussis katA was identified by complementation of UM255, a catalase-deficient strain of Escherichia coli. The nucleotide sequence of katA predicts a 55 kDa protein that shares homology with a class of haem-containing catalases found in both eubacteria and eukaryotes. Analysis of the nucleotide sequence upstream of katA revealed the presence of a copy of IS481, a B. pertussis-specific insertion sequence. The start site of transcription of katA was mapped to a T residue in IS481 by primer extension analysis performed with B. pertussis RNA and a katA-specific primer. A catalase-deficient strain of B. pertussis, DD900, was constructed by gene replacement. DD900 was more sensitive to killing by 1 and 5 mM H2O2 than the parental strain, BP339. However, there was no difference in the ability of DD900 and BP339 to survive for 2 h in human PMNs. This suggests that catalase plays no significant role in the survival of B. pertussis within PMNs.
...
PMID:Molecular characterization of catalase from Bordetella pertussis: identification of the katA promoter in an upstream insertion sequence. 783 May 50

Human dermal mast cells are capable of releasing cytokines, particularly preformed TNF alpha, upon appropriate stimulation. Mast cell activation in vivo was shown to be associated with an influx and activation of inflammatory cells, initially PMN (polymorphonuclear neutrophilic granulocytes) then eosinophils. In order to learn more about the mechanisms by which TNF alpha is capable of activating eosinophils, in the present study the effect of TNF alpha on morphology and function of highly purified normal eosinophils (> or = 95%) was examined. As estimated by transmission and scanning electron microscopy, TNF alpha-stimulated eosinophils appeared to be strictly adherent and flattened exhibiting a characteristic "hemispheric" shape. TNF alpha induced a dose-dependent, long-lasting production of reactive oxygen species as measured by lucigenin-dependent chemiluminescence (CL), even at a concentration of 0.001 U/ml. The maximal response upon stimulation with TNF alpha, however, was significantly lower than optimal effects induced by IL-5. TNF alpha-induced responses were completely inhibited by cytochalasin B and staurosporin, and partially blocked by pertussis toxin. Separation of eosinophils by discontinuous density gradients revealed the existence of at least two hypodense eosinophil populations with a distinct susceptibility to stimulation with TNF alpha. Based on functional assay systems, in contrast to a significant extracellular, only a small intracellular H2O2 production was detected. Accordingly, H2O2 production, detected by an ultrastructural technique, was observed only on the outer surface of the plasma membrane in the contact zones in between adjacent cells. Extracellular as well as intracellular production of H2O2 was completely inhibited by cytochalasin B. TNF alpha-induced activation of eosinophils is most probably mediated by binding to the 55 kD and the 75 kD TNF-receptor since both receptor molecules could be detected by FACS analysis and immune electron microscopy using receptor-specific antibodies. However, in contrast to its effect on eosinophil oxidative response, TNF alpha did not induce the release of significant concentrations of eosinophil cationic protein or eosinophil peroxidase in supernatants of cytokine-stimulated eosinophils, as detected by functional as well as immunological assay systems. These results clearly indicate that TNF alpha represents a potent eosinophil-activating cytokine which may be of relevance in the allergic inflammatory response.
...
PMID:TNF alpha-induced activation of eosinophil oxidative metabolism and morphology--comparison with IL-5. 800 Jul 7

The effects of diethyldithiocarbamate on superoxide release by rat neutrophils were investigated in a chemiluminescence study. Diethyldithiocarbamate augmented lucigenin-dependent chemiluminescence in a concentration-dependent manner and inhibited luminol-dependent chemiluminescence at concentrations of 0.1-1 microM. In contrast, after the addition of 0.1 mM diethyldithiocarbamate, the chemiluminescence was markedly enhanced. Diethyldithiocarbamate inhibited both the myeloperoxidase activity of neutrophils and the chemiluminescence generated in a cell-free horseradish peroxidase/H2O2 and H2O2/HOCl system. The increase in lucigenin-dependent chemiluminescence brought about by diethyldithiocarbamate was inhibited by H-7, ML-7, W-7, EGTA and pertussis toxin. These results suggest that diethyldithiocarbamate may stimulate O2- production by a guanosine 5'-triphosphate protein-mediated and Ca(2+)-dependent process and that the increase in O2- release by neutrophils may be dependent not only on the direct stimulation of the signal transduction pathway but also on the increase in O2- by reducing the effect of the hydroperoxide (H2O2)-myeloperoxidase system.
...
PMID:Effects of diethyldithiocarbamate on activating mechanisms of neutrophils. 809 Jul

Altered polymorphonuclear leukocyte (PMN) function is thought to contribute to organ dysfunction during the systemic inflammatory response syndrome (SIRS). To test this hypothesis, we evaluated whole blood PMN function adherent to fibronectin or laminin in patients with mild or severe acute pancreatitis as a paradigm for sirs. Whole-blood PMN intracellular H2O2 production, expression of CD32w (Fc gamma R II), CD16 (Fc gamma R III), and phagocytosis were performed using dichlorofluorescein diacetate, fluorescein isothiocyanate-labeled anti-CD32w, CD16, and serum-opsonized fluorescent microspheres. Group I (n x 7) represents normal control individuals; group II (n x 11) represents patients with mild acute pancreatitis. Group III (n x 15) represents critically ill patients with severe acute pancreatitis. Adherence of PMN from groups I and II to matrix proteins resulted in a 5% to 20% increase in each PMN function assayed whereas adherence of PMN from group III to matrix proteins resulted in 50% to 75% increases in each PMN function assayed. Pertussis toxin, pentoxifylline, and dibutyryl cyclic adenosine monophosphate (cAMP) each reduced group I-II H2O2 production and phagocytosis. Pentoxifylline and dibutyryl cAMP but not pertussis toxin reduced group III H2O2 production. Both intracellular H2O2 and phagocytosis assays from group III but not groups I-II showed exaggerated upregulation when exposed to NaF (4 mmol/L). Anti-interleukin-6 reduced the increase in intracellular H2O2 production in group III patients and significantly altered the exaggerated oxidative response to NaF. Longitudinal studies of group III whole-blood PMN showed persistent upregulation of intracellular H2O2 production in those patients whose hospital courses were complicated by multiple system organ failure. These results demonstrate abnormal whole blood PMN function during the systemic inflammatory response syndrome in the presence of fibronectin, or laminin and that this is mediated in part via a pertussis toxin insensitive altered guanosine triphosphate-binding protein.
...
PMID:Polymorphonuclear leukocyte dysregulation during the systemic inflammatory response syndrome. 811 41

In contrast to C5a, which represents a well-established potent activator of the respiratory burst in polymorphonuclear neutrophilic granulocytes (PMN), the functional role of C3a in the activation of PMN is, so far, poorly understood. Herein, the potential role of human C3a in the activation of the respiratory burst in human PMN was investigated. The release of reactive oxygen species (ROS) of PMN from healthy donors was measured by lucigenin-dependent chemiluminescence. C3a dose-dependently induced the production of ROS in human PMN in the range between 10 ng/mL and 1,000 ng/mL, whereas C3a-desArg was inactive. Flow cytometric measurement of H2O2 by dihydrorhodamine-123 labeling of anti-CD16-stained PMN showed that predominantly neutrophilic PMN are responsible for the C3a-induced activation of the respiratory burst. To exclude that C3a stimulation was caused by contamination with C5a, the specificity of C3a-induced activation of PMN was shown using monoclonal antibodies (MoAbs). Accordingly, the effect of C3a was completely abolished in the presence of Fab fragments of a blocking anti-C3a MoAb. In addition, blockade of the C5a receptor by the anti-C5a receptor (anti-C5aR) MoAb, S5/1, totally inhibited the C5a-induced production of ROS, whereas the C3a response in the presence of the anti-C5aR MoAb was unaffected. The specificity of the response was further confirmed by homologous desensitization after restimulation with C3a. In contrast, no cross-desensitization was observed upon stimulation with C5a. The C3a-induced ROS production by PMN was inhibited by pertussis toxin, indicating the involvement of guanine nucleotide-binding proteins (Gi proteins) in the signal transduction process initiated by C3a. In addition, stimulation of PMN by C3a resulted in a transient increase in the cytosolic free calcium concentration ([Ca2+]i) in a dose-dependent manner. In contrast to C3a-induced ROS production, C3a did not induce a chemotactic response in PMN, indicating functional qualitative differences as compared with C5a. In summary, these results show that C3a is a potent activator of the respiratory burst in human PMN. Therefore, these findings point to a novel role of C3a in the pathogenesis of inflammatory diseases associated with increased C3a levels and PMN activation.
...
PMID:C3a activates the respiratory burst in human polymorphonuclear neutrophilic leukocytes via pertussis toxin-sensitive G-proteins. 819 68

Neutrophils produce large quantities of HOCl when stimulated by surface-associated immunoglobulin G, a result not seen when neutrophils are stimulated with soluble complexes of IgG. Compared with unactivated cells or cells stimulated with soluble aggregates of IgG, a significant influx of extracellular 45Ca2+ was observed in cells activated by surface-associated IgG. Removal of extracellular calcium with EGTA almost completely blocked HOCl production. Similarly, treatment of neutrophils with lanthanum, which has been shown to interfere with calcium channels, also effectively blocked HOCl production. These results were not secondary to an overall decrease in activation, as superoxide production and release of the specific granule protein lactoferrin and the azurophilic granule protein myeloperoxidase were not significantly altered by lanthanum or EGTA. Production of H2O2, the precursor of HOCl, was similarly decreased by both EGTA and lanthanum. Induction of extracellular calcium influx with a calcium ionophore in the presence of soluble aggregates of IgG resulted in HOCl production. Production of HOCl is not sensitive to inhibition by pretreatment of cells with pertussis toxin. These observations indicate that the differences in the biological responses of human neutrophils to surface-associated IgG compared with soluble aggregates of IgG are associated with differing signaling events, including influx of extracellular calcium.
...
PMID:HOCl production by human neutrophils activated by surface-associated IgG: requirement for influx of extracellular calcium. 819 5

It is well demonstrated that various peptides derived from elastin are biologically active. The hexapeptide (Val-Gly-Val-Ala-Pro-Gly; VI) as well as elastin peptides were demonstrated to be chemotactic for fibroblasts, while kappa-elastin had marked biological effects on human PMNLs. The aim of our present work was to synthesize various elastin peptides and compare their action to that of kappa-elastin and this hexapeptide. The results indicate that the hexapeptide (Val-Gly-Val-Ala-Pro-Gly) and the two other synthesized hexapeptides (Pro-Gly-Val-Gly-Val-Ala; III and Val-Gly-Val-Gly-Val-Ala; IV) had very similar and specific effects on intracellular free calcium metabolism, on superoxide anion production and elastase release. The other peptides had no effects on these parameters, except a tripeptide (Val-Gly-Val; V) on superoxide anion production. Moreover, the effect of the hexapeptides (III and VI) could be abolished by Pertussis toxin preincubation. All peptides had very similar stimulating effects on H2O2 production and myeloperoxidase release. We conclude that most probably the peptide size and conformation, as well as peptide composition play a role in the biological effects of these peptides, through specific receptors on PMNLs surface.
...
PMID:Effects of synthesized elastin peptides on human leukocytes. 865 87

<< Previous 1 2 3 4 Next >>