UMLS:C0043167 - FACTA Search

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

Immunization of common marmosets (Callithrix jacchus) with a single dose of human myelin in CFA, without administration of Bordetella pertussis, induces a form of autoimmune encephalomyelitis (EAE) resembling in its clinical and pathological expression multiple sclerosis in humans. The EAE incidence in our outbred marmoset colony is 100%. This study was undertaken to assess the genetic and immunological basis of the high EAE susceptibility. To this end, we determined the separate contributions of immune reactions to myelin/oligodendrocyte glycoprotein (MOG) and myelin basic protein to the EAE induction. Essentially all pathological features of myelin-induced EAE were also found in animals immunized with MOG in CFA, whereas in animals immunized with myelin basic protein in CFA clinical and pathological signs of EAE were lacking. The epitope recognition by anti-MOG Abs and T cells were assessed. Evidence is provided that the initiation of EAE is based on T and B cell activation by the encephalitogenic phMOG14-36 peptide in the context of monomorphic Caja-DRB*W1201 molecules.
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PMID:Myelin/oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis in common marmosets: the encephalitogenic T cell epitope pMOG24-36 is presented by a monomorphic MHC class II molecule. 1087 88

An antitumor glycoprotein [streptococcal acidic glycoprotein (SAGP)] purified from an extract of Streptococcus pyogenes inhibited the growth of human epidermoid carcinoma A431 cells overexpressing epidermal growth factor receptor (EGFR) in a time- and a concentration-dependent manner. The antiproliferative effect of SAGP was diminished by preincubating the cells with pertussis toxin and by coadministration of sodium orthovanadate, an inhibitor of protein tyrosine phosphatases (PTPases). Western blot analysis showed that the immunoreactivity of a M(r) 170,000 band of cell lysate to antiphosphotyrosine antibody was reduced by SAGP, and the effect was abolished by sodium orthovanadate. The phosphotyrosine level of the precipitant with anti-EGFR antibody was reduced by SAGP, which was abolished by preincubation with pertussis toxin or by a coadministration with sodium orthovanadate. The PTPase activity transiently increased in the lysate of cells incubated with SAGP and was inhibitable by sodium orthovanadate. Additionally, preincubation of serum-starved A431 cells with SAGP decreased the epidermal growth factor-induced tyrosine phosphorylation of EGFR, and the effect of SAGP was sodium orthovanadate sensitive. These findings indicate that dephosphorylation of the M(r) 170,000 EGFR by activation of PTPase(s) may be responsible in part for the antiproliferative effect of SAGP on A431 cells.
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PMID:Growth-inhibitory effect of a streptococcal antitumor glycoprotein on human epidermoid carcinoma A431 cells: involvement of dephosphorylation of epidermal growth factor receptor. 1150 66

Human immunodeficiency virus type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry. It was recently demonstrated that HIV-1 glycoprotein 120 (gp120) elevated calcium and activated several ionic signaling responses in primary human macrophages, which are important targets for HIV-1 in vivo. This study shows that chemokine receptor engagement by both CCR5-dependent (R5) and CXCR4-dependent (X4) gp120 led to rapid phosphorylation of the focal adhesion-related tyrosine kinase Pyk2 in macrophages. Pyk2 phosphorylation was also induced by macrophage inflammatory protein-1beta (MIP-1beta) and stromal cell-derived factor-1alpha, chemokine ligands for CCR5 and CXCR4. Activation was blocked by EGTA and by a potent blocker of calcium release-activated Ca++ (CRAC) channels, but was insensitive to pertussis toxin (PTX), implicating CRAC-mediated extracellular Ca++ influx but not Galpha(i) protein-dependent mechanisms. Coreceptor engagement by gp120 and chemokines also activated 2 members of the mitogen-activated protein kinase (MAPK) superfamily, c-Jun amino-terminal kinase/stress-activated protein kinase and p38 MAPK. Furthermore, gp120-stimulated macrophages secreted the chemokines monocyte chemotactic protein-1 and MIP-1beta in a manner that was dependent on MAPK activation. Thus, the gp120 signaling cascade in macrophages includes coreceptor binding, PTX-insensitive signal transduction, ionic signaling including Ca++ influx, and activation of Pyk2 and MAPK pathways, and leads to secretion of inflammatory mediators. HIV-1 Env signaling through these pathways may contribute to dysregulation of uninfected macrophage functions, new target cell recruitment, or modulation of macrophage infection.
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PMID:HIV-1 gp120 and chemokine activation of Pyk2 and mitogen-activated protein kinases in primary macrophages mediated by calcium-dependent, pertussis toxin-insensitive chemokine receptor signaling. 1169 70

The alpha chemokine receptor CXCR4 is used as the major coreceptor for the cell entry of T-cell-tropic human immunodeficiency virus-1 (HIV-1) isolates. Activation of this coreceptor by its natural ligand SDF1alpha is associated with an intracellular Ca(2+) increase. Because the HIV-1 glycoprotein 120 (gp120) is shedded from the surface of HIV-1-infected cells and is regarded as an injurious molecule in the pathogenesis of HIV-1-associated encephalopathy (HIVE), we investigated the effects of gp120 on the intracellular Ca(2+) regulation of astrocytes and neurons. After 5 days in vitro (DIV), SDF1alpha (50 nM) elicited a pertussis toxin-sensitive intracellular Ca(2+) increase due to Ca(2+) release from internal stores that was reduced by a blocking monoclonal antibody against the CXCR4 receptor in astrocytes and neurons. Parallel with the development of the SDF1alpha response, cells became sensitive to direct application of gp120 (1.25 microg/ml), which, similarly to SDF1alpha, elicited a transient intracellular Ca(2+) increase. However, short-term incubation with gp120 for 60 to 120 min induced a reduction of glutamate- or ATP-evoked intracellular Ca(2+) responses only in astrocytes and not in neurons, although functional CXCR4 receptors were expressed in both cell types. Therefore, our data strongly suggest that the CXCR4 receptor-mediated intracellular signaling pathway of gp120 differs in astrocytes and neurons.
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PMID:Functional CXCR4 receptor development parallels sensitivity to HIV-1 gp120 in cultured rat astroglial cells but not in cultured rat cortical neurons. 1240 67

The mammalian sperm acrosome reaction (AR) is essential to fertilization and is believed to be initiated in vivo by ZP3, a glycoprotein component of the egg zona pellucida (ZP). Recently, we reported the results of antagonist studies suggesting that a nicotinic acetylcholine receptor (nAChR) containing an alpha7 subunit (alpha7nAChR) plays a role in the human sperm AR initiated by recombinant human ZP3 or by acetylcholine (ACh). Here, we show that ACh can initiate the mouse sperm AR and that antagonists of the nAChR inhibit the AR initiated by ACh or by ZP obtained from ovarian oocytes (isolated heat-solubilized mouse ZP). Preincubation with three antagonists of the nAChR, alpha-bungarotoxin (100 nM), alpha-conotoxin IMI (100 nM), and methyllycaconitine (100 nM), significantly blocked AR initiation by ACh or by isolated heat-solubilized mouse ZP (P </= 0.002). Because the only nAChR subunit known to bind all three antagonists is the alpha7, an alpha7nAChR appears to be involved in the mouse sperm AR initiated by mouse ZP or by ACh. The nAChR antagonists did not inhibit the AR initiated by calcium ionophore A23187, suggesting that the role of alpha7nAChR is upstream from Ca2+ influx. Pertussis toxin (PTX, 100 ng/ml) did not inhibit the AR initiated by ACh, suggesting that the alpha7nAChR might be a candidate for the PTX-insensitive, poorly selective cation channel shown previously to play a role in ZP-initiated mouse sperm AR. These studies with mouse sperm and ovary-derived ZP strongly support our previous conclusion that activation of an alpha7nAChR is important to the mammalian AR initiated by the egg ZP.
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PMID:Evidence suggesting that the mouse sperm acrosome reaction initiated by the zona pellucida involves an alpha7 nicotinic acetylcholine receptor. 1260 7

Experimental Autoimmune Encephalomyelitis (EAE) can be induced in mice of the C57BL/6 strain by subcutaneous immunization with myelin/oligodendrocyte glycoprotein (MOG) peptide p35-55 in CFA, administered twice at an interval of one week and supplemented with Bordetella pertussis toxin given IV. Here, we studied the effect on the induction of EAE of depleting antibodies to CD4, CD8, or CD25 administered before either the first or the second dose of MOG p35-55. We found that anti-CD4 abolished EAE when given before the first immunization; anti-CD4 did not affect the disease when it was given before the second immunization. Anti-CD8 enhanced EAE induction when given before either of the two immunizations. Anti-CD25 enhanced EAE to the same degree as anti-CD8 when given before the first immunization, but anti-CD25 was even more effective in enhancing EAE when given before the second immunization. The anti-CD25 treatment led to significantly enhanced IFNgamma production by T cells responding to MOG p35-55 and persisting anti-MOG antibodies detectable 56 days after the first immunization. Administration of anti-CD8 or anti-CD25 abolished the need for pertussis toxin to induce EAE. These findings are compatible with the idea that CD4 T cells are required for the initial induction of EAE and that the disease is down-regulated by T cells expressing CD8 or CD25. These regulatory T cells exist prior to MOG immunization, but the CD25+ regulators appear to be further amplified by immunization.
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PMID:Regulation of experimental autoimmune encephalomyelitis by CD4+, CD25+ and CD8+ T cells: analysis using depleting antibodies. 1523 47

Adenylate cyclase (AC) toxin is present on the surface of Bordetella pertussis organisms and their addition to eukaryotic cells results in increases in intracellular cAMP. To test the hypothesis that surface-bound toxin is the source for intoxication of cells when incubated with B. pertussis, we characterized the requirements of intoxication from intact bacteria and found that this process is calcium-dependent and blocked by monoclonal antibody to AC toxin or antibody against CD11b, a surface glycoprotein receptor for the toxin. Increases in intracellular cAMP correlate with the number of adherent bacteria, not the total number present in the medium, suggesting that interaction of bacteria with target cells is important for efficient delivery of AC toxin. A filamentous haemagglutinin-deficient mutant (BP353) and a clinical isolate (GMT1), both of which have a marked reduction in AC toxin on their surface, and wild-type B. pertussis (BP338) from which surface AC toxin has been removed by trypsin, were fully competent for intoxicating target cells, demonstrating that surface-bound AC toxin is not responsible for intoxication. B. pertussis killed by gentamicin or gamma irradiation were unable to intoxicate, illustrating that toxin delivery requires viable bacteria. Furthermore, CCCP, a protonophore that disrupts the proton gradient necessary for the secretion of related RTX toxins, blocked intoxication by whole bacteria. These data establish that delivery of this toxin by intact B. pertussis is not dependent on the surface-associated AC toxin, but requires close association of live bacteria with target cells and the active secretion of AC toxin.
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PMID:Newly secreted adenylate cyclase toxin is responsible for intoxication of target cells by Bordetella pertussis. 1534 49

To facilitate our understanding of the role of zona pellucida glycoproteins during fertilization in humans, recombinant human zona pellucida glycoprotein-A (hZPA), -B (hZPB) and -C (hZPC) were obtained by using Escherichia coli and baculovirus expression systems. Analysis by SDS-PAGE and Western blot of the Ni-NTA affinity purified recombinant proteins revealed that the baculovirus-expressed hZPA, hZPB and hZPC have an apparent molecular weight of approximately 110, approximately 70-75 and approximately 65 kDa, respectively, as compared to approximately 80, approximately 65 and approximately 50 kDa of the respective E. coli-expressed proteins. Lectin binding studies revealed that the baculovirus-expressed recombinant zona proteins were glycosylated. Major oligosaccharides were represented by strong reactivity with Concanavalin A (mannose alpha 1-3 or mannose alpha 1-6 residues) and Jacalin (alpha-O glycosides of Gal or GalNAc moieties). A significant increase in acrosomal exocytosis was observed when capacitated human sperm were incubated in vitro with baculovirus-expressed hZPB (P=0.0005) and hZPC (P=0.0005) The E. coli-expressed hZPB, hZPC and baculovirus-expressed hZPA failed to induce any significant increase (P>0.05) in acrosome reaction. In contrast to hZPC, the acrosome reaction induced by recombinant hZPB was not inhibited by pertussis toxin. These studies, for the first time, have demonstrated that in humans, ZPB also induces acrosomal exocytosis through a Gi independent pathway.
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PMID:Baculovirus-expressed recombinant human zona pellucida glycoprotein-B induces acrosomal exocytosis in capacitated spermatozoa in addition to zona pellucida glycoprotein-C. 1580 45

Thrombospondin-1 (THBS1) is a large extracellular matrix glycoprotein that affects vasculature systems such as platelet activation, angiogenesis, and wound healing. Increases in THBS1 expression have been liked to disease states including tumor progression, atherosclerosis, and arthritis. The present study focuses on the effects of thrombin activation of the G-protein-coupled, protease-activated receptor-1 (PAR-1) on THBS1 gene expression in the microvascular endothelium. Thrombin-induced changes in gene expression were characterized by microarray analysis of approximately 11,000 different human genes in human microvascular endothelial cells (HMEC-1). Thrombin induced the expression of a set of at least 65 genes including THBS1. Changes in THBS1 mRNA correlated with an increase in the extracellular THBS1 protein concentration. The PAR-1-specific agonist peptide (TFLLRNK-PDK) mimicked thrombin stimulation of THBS1 expression, suggesting that thrombin signaling is through PAR-1. Further studies showed THBS1 expression was sensitive to pertussis toxin and protein kinase C inhibition indicating G(i/o)- and G(q)-mediated pathways. THBS1 up-regulation was also confirmed in human umbilical vein endothelial cells stimulated with thrombin. Analysis of the promoter region of THBS1 and other genes of similar expression profile identified from the microarray predicted an EBOX/EGRF transcription model. Expression of members of each family, MYC and EGR1, respectively, correlated with THBS1 expression. These results suggest thrombin formed at sites of vascular injury increases THBS1 expression into the extracellular matrix via activation of a PAR-1, G(i/o), G(q), EBOX/EGRF-signaling cascade, elucidating regulatory points that may play a role in increased THBS1 expression in disease states.
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PMID:Thrombin modulates the expression of a set of genes including thrombospondin-1 in human microvascular endothelial cells. 1581 47

Mammalian fertilization is initiated by the species-specific binding of sperm to the zona pellucida, or egg coat. Earlier studies suggested that sperm-egg adhesion in mouse is mediated by the binding of beta1,4-galactosyltransferase-I (GalT) on the sperm surface to specific glycoside ligands on the egg coat glycoprotein, ZP3. Binding of multiple ZP3 oligosaccharides induces GalT aggregation, triggering a pertussis toxin-sensitive G-protein cascade leading to induction of the acrosome reaction. Consistent with this, sperm bearing targeted deletions in GalT are unable to bind ZP3 nor undergo ZP3-dependent acrosomal exocytosis; however, GalT-null sperm are still able to bind to the egg coat. This indicates that sperm-egg binding requires at least two independent binding mechanisms: a GalT-ZP3-independent event that mediates initial adhesion, followed by a GalT-ZP3 interaction that facilitates acrosomal exocytosis. During the past few years, novel GalT-ZP3-independent gamete receptors have been identified that appear to participate in initial gamete adhesion. On such receptor is SED1, an EGF repeat and discoidin domain protein that coats sperm as they traverse through the epididymis, and which is required for sperm to bind the egg coat. Similarly, a novel egg coat ligand is present on ovulated oocytes, but not on ovarian eggs, and which also appears to function in initial sperm binding. The identification of novel gamete receptors that are required for sperm-egg binding opens up new avenues for the development of specific contraceptive strategies.
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PMID:Identification of novel gamete receptors that mediate sperm adhesion to the egg coat. 1641 65

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