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)

We have examined the role of 12 polymorphic residues of the beta-chain of the HLA-DR1 class II molecule in T cell recognition of an epitope of pertussis toxin. Murine L cell transfectants expressing wild-type or mutant DR1 molecules (containing single amino acid substitutions in DR(beta 1*0101)) were used as APC in proliferation assays involving nine DR1-restricted T cell clones specific for peptide 30-42 of pertussis toxin. Four different patterns of recognition of the mutants were found among the pertussis-specific clones. Residues in the third hypervariable region (HVR) of DR(beta 1*0101) are critically important for all the T cell clones; amino acid substitutions at positions 70 and 74 abrogated recognition by all of the T cell clones, and substitutions at positions 67 and 71 eliminated recognition by most of the clones. In contrast, most single amino acid substitutions in the first and second HVR, predicted to be located in the floor of the peptide binding groove, had little or no effect on the proliferative responses of these clones. However, the involvement of beta-chain first and second HVR residues was demonstrated by the inability of transfectants expressing wild-type DR(beta 1*0404) (DR4Dw14) or DR(beta 1*1402) (DR6Dw16) to present peptide to these clones. These beta-chains have completely different first and second HVR compared with DR(alpha,beta 1*0101) although the third HVR are identical. These results illustrate the functional importance of third HVR residues of DR(beta 1*0101) and allow definition of the molecular interactions of the DR1 molecule with the 30-42 peptide.
...
PMID:Mutations in the third, but not the first or second, hypervariable regions of DR(beta 1*0101) eliminate DR1-restricted recognition of a pertussis toxin peptide. 157 65

The adrenergic agonist norepinephrine is shown to stimulate endothelium to induce protein S release and degradation, leading to diminished anti-coagulant activity and to down-regulation of protein S cell surface-binding sites. Norepinephrine-induced release of intracellular protein S was blocked by the alpha 1-adrenergic antagonist prazosin (10(-7) M) but not by the alpha-adrenergic antagonist propranolol (10(-6) M) or the alpha 2-adrenergic antagonist yohimbine (10(-5) M) indicating that this response resulted from the specific interaction of norepinephrine with a class of alpha 1-adrenergic receptors not previously observed on endothelium. Attenuation of norepinephrine-induced release of protein S by pertussis toxin in association with the ADP-ribosylation of a 41,000-D membrane protein indicates that this intracellular transduction pathway involves a regulatory G protein. The observation that protein S was released from endothelium in response to maneuvers which elevate intracellular calcium or activate protein kinase C suggests that the response may be mediated via intermediates generated through the hydrolysis of phosphoinositides. Morphologic studies were consistent with a mechanism in which norepinephrine causes exocytosis of vesicles containing protein S. In addition to release of protein S, norepinephrine also induced loss of endothelial cell protein S-binding sites, thereby blocking effective activated protein C-protein S-mediated factor Va inactivation on the cell surface. Norepinephrine-mediated endothelial cell stimulation thus results in loss of intracellular protein S and suppression of cell surface-binding sites, modulating the anti-coagulant protein C pathway on the vessel wall. These studies define a new relationship between an anti-coagulant mechanism and the autonomic nervous system, and indicate a potential role for an heretofore unrecognized class of alpha 1-adrenergic receptors in the regulation of endothelial cell physiology.
...
PMID:Norepinephrine down-regulates the activity of protein S on endothelial cells. 296 46

Addition of gonadotropin releasing hormone (GnRH) to pituitary cells prelabeled with [32P]Pi or with myo-[2-3H]inositol, resulted in a rapid decrease in the level of [32P]phosphatidylinositol 4,5-bisphosphate (approximately 10 s), and in [32P]phosphatidylinositol 4-phosphate (approximately 1 min), followed by increased labeling of [32P]phosphatidylinositol and [32P]phosphatidic acid (1 min). GnRH stimulated the appearance of [3H]myo-inositol 1,4,5-trisphosphate (10 s), [3H]myo-inositol 1,4-bisphosphate (15 s), and [3H]myo-inositol 1-phosphate (1 min) in the presence of Li+ (10 mM). Li+ alone stimulated the accumulation of [3H]myo-inositol 1-phosphate and [3H]myo-inositol 1,4-bisphosphate but not [3H]myo-inositol 1,4,5-trisphosphate, but had no effect on luteinizing hormone release. The effect of GnRH on inositol phosphates (Ins-P) production was dose-related (ED50 = 1-5 nM), and was blocked by a potent antagonist [D-pGlu,pClPhe,D-Trp]GnRH. Elevation of cytosolic free Ca2+ levels ([Ca2+]i), by ionomycin and A23187 from intracellular or extracellular Ca2+ pools, respectively, had no significant effect on [3H]Ins-P production. GnRH-induced [3H]Ins-P production was not dependent on extracellular Ca2+ and was noticed also after extracellular or intracellular Ca2+ mobilization by A23187 or ionomycin, respectively. The effect of GnRH on [3H]Ins-P accumulation was not affected by prior treatment of the cells with the tumor promoter phorbol ester 12-O-tetradecanoylphorbol-13-acetate or with islet-activating protein pertussis toxin. These results indicate that GnRH stimulates a rapid phosphodiester hydrolysis of polyphosphoinositides. The stimulatory effect is not mediated via an islet-activating protein-substrate, is not dependent on elevation of [Ca2+]i, neither is it negatively regulated by 12-O-tetradecanoylphorbol-13-acetate which activates Ca2+/phospholipid-dependent protein C kinase. The results are consistent with the hypothesis that GnRH-induced phosphoinositide turnover is responsible for Ca2+ mobilization followed by gonadotropin release.
...
PMID:Gonadotropin-releasing hormone activates a rapid Ca2+-independent phosphodiester hydrolysis of polyphosphoinositides in pituitary gonadotrophs. 301 78

Among bacterial toxins, the adenylate cyclase toxin of Bordetella pertussis (CyaA) has a unique mechanism of entry that consists in the direct translocation of its catalytic domain across the plasma membrane of target cell, a mechanism supposed to be independent of any endocytic pathway. Here, we report that the CyaA toxin is delivered to the cytosolic pathway for MHC class I-restricted Ag presentation. Using peritoneal macrophages as APC, we show that the OVA 257-264 CD8+ epitope genetically inserted into a detoxified CyaA (CyaA-OVA E5) is presented to CD8+ T cells by a mechanism requiring 1) proteasome processing, 2) TAP, and 3) neosynthesis of MHC class I. We demonstrate that the presentation of CyaA-OVA E5, like the translocation of CyaA into eukaryotic cells, is dependent on extracellular Ca2+ and independent of vacuolar acidification. Moreover, inhibitors of the phagocytic and macropinocytic endocytic pathways do not affect the CyaA-OVA E5 presentation. The absence of specific cellular receptors for CyaA correlates with the ability of various APC to present the recombinant CyaA toxin, including dendritic cells, macrophages, splenocytes, and lymphoid tumoral lines. Taken together, our results show that the CyaA presentation pathway is not cell type specific and is unrelated to a defined type of endocytic mechanism. Thus, it represents a new and unconventional delivery of an exogenous Ag into the conventional cytosolic pathway.
...
PMID:Direct delivery of the Bordetella pertussis adenylate cyclase toxin to the MHC class I antigen presentation pathway. 997 58

Pertussis toxin (PT) has been shown to act as an adjuvant that enhances the production of both Th1 and Th2 cytokines to coinjected protein antigens. It has remained unresolved, however, how PT affects the clonal sizes, long-term effector functions, and Th1/Th2/Th0 differentiation of the T cell responses induced. We have studied the effects of PT on the development of the CD4(+) T cell response to a prototypic antigen, hen eggwhite lysozyme (HEL). HEL injection with incomplete Freund's adjuvant (IFA) resulted in an IFN-gamma(-)/IL-5(+) Th2 recall response. In comparison, co-administration of PT with HEL:IFA enhanced the frequencies of IL-5-producing T cells up to eightfold, and induced the differentiation of high frequencies of IFN-gamma-producing CD4(+) T cells. The results showed that the IFN-gamma and IL-5 produced, originated from clonally expanded Th1 and Th2, but not Th0 cells, and that the effector functions of long-term memory cells were unaffected. Adoptive transfer experiments suggested that PT mediated these effects via activation of APC, not by acting on the T cells directly. The effects of PT on the developing T cell response required the presence of the holotoxin (A- and B-subunit); the individual subunits did not show adjuvant effects. The data suggest that PT enhanced cytokine production by promoting differentiation and vigorous clonal expansion of Th1 and Th2 cells via activation of APC.
...
PMID:The enhanced antigen-specific production of cytokines induced by pertussis toxin is due to clonal expansion of T cells and not to altered effector functions of long-term memory cells. 1094 Sep 34

The C-terminal portion of G(alpha) proteins plays a key role in their selective activation by cognate receptors. alpha(2A)-Adrenoceptors (alpha(2A)-ARs) can differentially inhibit or stimulate adenylyl cyclases by the activation of distinct G(i/o) and G(s) protein families. The implication of the C-terminal portion of G(alpha o) and G(alphas) proteins in their activation by alpha(2A)-ARs was analyzed by constructing mutant G(alpha o) proteins in which each of the last five amino acid positions were exchanged for those corresponding to a G(alphas) protein. Agonist-dependent, pertussis toxin-resistant binding of guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTP gamma S) revealed that the degree of positive efficacy of clonidine was highly dependent on the presence of a G(alpha o) protein-derived Gly amino acid as the -3 residue at the C-terminal portion of the protein. In contrast, antagonist properties for clonidine were observed for those mutants carrying a G(alphas) protein-derived Glu residue at this position. (-)-Epinephrine yielded almost similar maximal [(35)S]GTP gamma S binding responses, but its potency was decreased 22- to 150-fold at the -3 Glu containing mutant G(alpha o) proteins compared with those mutants containing a Gly. A 9- to 39-fold increase in the alpha(2A)-AR agonist equilibrium dissociation constants further reflected changes in the G(alpha) protein-induced alpha(2A)-AR state mediated by the specific Gly to Glu mutation in the C-terminal portion of the G(alpha o) protein. The present data emphasize the unique role of the -3 position at the G(alpha) protein C-terminal portion, independent of its surrounding peptidic environment, in constraining a structure favorable for activated receptor interaction and transmission of the mutation-induced conformational change from the G(alpha o) protein to the alpha(2A)-AR.
...
PMID:Reciprocal modulation of alpha(2A)-adrenoceptor and G(alpha o) protein states as determined by carboxy-terminal mutagenesis of a G(alpha o) protein. 1156 27

The humoral response of mice and rabbits to the injection of whole-cell pertussis vaccine (PV) and acellular pertussis vaccine (APV), developed at the Mechnikov Research Institute for Vaccines and Sera (Russian Acad. Med. Sci.) in Moscow, was studied. In the sera of immunized animals antibodies to the antigenic complex were determined in the direct hemagglutination (DHA) test, specific antibodies to filamentous hemagglutinin (FHA) and pertussis toxin (PT)--in the enzyme immunoassay (EIA) and antibodies neutralizing PT in a cytopathogenic dose (CPD)--in neutralization test on Chinese hamster ovary (CHO) cells. In mice and rabbits immunized with APV the antibody titers determined in the DHA test were higher than those in the animals immunized with PV. Specific antibodies titers to FHA and PT in the sera of rabbits immunized with APV were also higher than those in the sera of rabbits immunized with PV. High dilutions of sera taken from the animals immunized with APC neutralized 4-16 doses of PT in the neutralization test on CHO cells. The most important result of this study was the detection of a more pronounced immune response in the animals immunized with APV in comparison with that induced by PV according to the results obtained in EIA and in the test of PT CPD neutralization on CHO cells.
...
PMID:[Humoral response to the injection of acellular Pertussis vaccine]. 1188 94

Host resistance to the intracellular protozoan Toxoplasma gondii is highly dependent on early IL-12 production by APC. We demonstrate here that both host resistance and T. gondii-induced IL-12 production are dramatically reduced in mice lacking the adaptor molecule MyD88, an important signaling element used by Toll-like receptor (TLR) family members. Infection of MyD88-deficient mice with T. gondii resulted in uncontrolled parasite replication and greatly reduced plasma IL-12 levels. Defective IL-12 responses to T. gondii Ags (soluble tachyzoite Ag (STAg)) were observed in MyD88(-/-) peritoneal macrophages, neutrophils, and splenic dendritic cells (DC). In contrast, DC from TLR2- or TLR4-deficient animals developed normal IL-12 responses to STAg. In vivo treatment with pertussis toxin abolished the residual IL-12 response displayed by STAg-stimulated DC from MyD88(-/-) mice. Taken together, these data suggest that the induction of IL-12 by T. gondii depends on a unique mechanism involving both MyD88 and G protein-coupled signaling pathways.
...
PMID:Cutting edge: MyD88 is required for resistance to Toxoplasma gondii infection and regulates parasite-induced IL-12 production by dendritic cells. 1205 6

Pertussis toxin (PTx), an exotoxin produced by Bordetella pertussis, has long been used as a mucosal adjuvant. We examined the T cell stimulatory properties of PTx in order to dissect its mechanisms of adjuvanticity. PTx or the B-oligomer of PTx (PTxB) failed to activate purified murine CD4+ or CD8+ T cells, as measured by a lack of proliferation or expression of early T cell activation markers. However, these T cells proliferated extensively in response to the toxin in the presence of syngeneic DC, and proliferation was accompanied by a high level of IFN-gamma production in the absence of IL-12. Interestingly, such responses were independent of signals mediated by MHC-TCR interaction. Both PTx and PTxB were found to bind stably to the surface of DC, and increased the adherence of DC to surrounding cells. These data suggest that polyclonal T cell responses mediated by the toxin are likely to be caused by the toxin bound on the surface of APC, either cross-linking cell surface molecules on T cells, or directly stimulating T cells together with the co-stimulatory molecules expressed on APC. B. pertussis may use this toxin as a mechanism to evade a specific immune response.
...
PMID:Cell-surface bound pertussis toxin induces polyclonal T cell responses with high levels of interferon-gamma in the absence of interleukin-12. 1281 46

To determine the value of gene markers for surveillance and to assess the genetic stability of potential acellular pertussis vaccine components, the sequence variation in ten virulence-related genes of Bordetella pertussis was investigated in strains isolated in the UK between 1920 and 2002. These genes encode: pertactin (prnA); pertussis toxin subunits S1 (ptxA) and S3 (ptxC); tracheal colonization factor (tcfA); bordetella autotransporter protein C (bapC); bordetella resistance to killing protein (brkA); fimbrial antigen 2 (fim2); outer-membrane protein Q (ompQ); virulence-activated gene 8 (vag8) and adenylate cyclase toxin (cyaA). The encoded proteins are either components of current acellular vaccines (ACVs), or potential virulence markers for B. pertussis. Three strains used in the pertussis UK whole-cell vaccine (WCV), strain Tohama-I used for production of ACV components and the type strain of B. pertussis (18323(T)) were also analysed. Several novel alleles were found. The UK isolates were assigned multi-locus sequence types (MLSTs) according to a previously described scheme for B. pertussis based on three of these genes (ptxA, ptxC and tcfA). Compared with isolates from other countries, the UK clinical strains showed a distinct distribution of MLSTs. Apart from one strain that was MLST-3, all other recent isolates (2000-2002) were identified as MLST-5. These isolates differed from the three WCV strains, which were MLST-2 or MLST-3, the Tohama-I strain (MLST-2) and the type strain of B. pertussis (MLST-9). MLST-3 and MLST-5 differ only by a single synonymous mutation, but this method does indicate that currently circulating strains of B. pertussis are not identical to the vaccine types, and they may differ in other important characteristics. Two new MLSTs were identified amongst historical UK isolates. Sequence-based typing offers a convenient method of analysing and comparing populations of B. pertussis from different time periods and from different countries. The variation exhibited by prnA and fim2 suggests that they could be useful, additional epidemiological markers in such a typing scheme.
...
PMID:Sequence variation and conservation in virulence-related genes of Bordetella pertussis isolates from the UK. 1509 43

1 2 3 Next >>