Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 69-kDa protein has been identified on the surface of the Gram-negative pathogen Bordetella pertussis that can elicit a protective immune response in animal models. This protein is associated with virulent strains of B. pertussis but its function has remained unclear. In this report we demonstrate that purified preparations of the 69-kDa outer membrane protein can promote the attachment of Chinese hamster ovary (CHO) cells. The interaction between the mammalian cells and this protein can be specifically inhibited by an Arg-Gly-Asp (RGD)-containing synthetic peptide that is homologous with a region found in the 69-kDa protein sequence. These studies indicate that a specific cell binding site containing an Arg-Gly-Asp sequence may be involved in the interaction of this bacterial protein with mammalian cell surfaces. To further investigate the role of this protein as a bacterial adhesin, a mutant of B. pertussis W28 that does not express the 69-kDa protein was constructed using the plasmid vector pRTP1. This mutant was 30-40% less efficient at adhering to CHO cells and to human HeLa cells than was the parent strain. These data support a role for this 69-kDa outer membrane protein in the attachment of B. pertussis to mammalian cells. We propose the name "pertactin" for this protein.
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PMID:Pertactin, an Arg-Gly-Asp-containing Bordetella pertussis surface protein that promotes adherence of mammalian cells. 198 35

The adherence of Bordetella pertussis to human respiratory cilia is critical to the pathogenesis of whooping cough but the significance of bacterial attachment to macrophages has not been determined. Adherence to cilia and macrophages is mediated by two large, nonfimbrial bacterial proteins, filamentous hemagglutinin (FHA), and pertussis toxin (PT). PT and FHA both recognize carbohydrates on cilia and macrophages; FHA also contains an Arg-Gly-Asp (RGD) sequence which promotes bacterial association with the macrophage integrin complement receptor 3 (CR3). We determined that virulent B. pertussis enter and survive in mammalian macrophages in vitro and that CR3 is important for this uptake process. We then determined the relative contribution of CR3 versus carbohydrate-dependent interactions to in vivo pulmonary colonization using a rabbit model. B. pertussis colonized the lung as two approximately equal populations, one extracellular population attached to ciliary and macrophage surface glycoconjugates and another population within pulmonary macrophages. Loss of the CR3 interaction, either by mutation of FHA or treatment with antibody to CR3, disrupted accumulation of viable intracellular bacteria but did not prevent lung pathology. In contrast, elimination of carbohydrate-bound bacteria, either by a competitive receptor analogue or an anti-receptor antibody, was sufficient to prevent pulmonary edema. We propose that CR3-dependent localization of B. pertussis within macrophages promotes persistence of bacteria in the lung without pulmonary injury. On the other hand, the presence of extracellular bacteria adherent to cilia and macrophages in carbohydrate-dependent interactions is associated with pulmonary pathology.
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PMID:Integrin-mediated localization of Bordetella pertussis within macrophages: role in pulmonary colonization. 202 24

Proteins can be post-translationally modified by ADP-ribose. Previously, two classes of ADP-ribosyl protein linkages have been detected in vivo which have chemical properties indistinguishable from ADP-ribosyl arginine and ADP-ribosyl glutamate or aspartate. Reported here is the detection of a third class of endogenous ADP-ribosyl protein linkage. This class is chemically indistinguishable from ADP-ribose linked to cysteine residues by a thioglycosidic bond. The distribution of ADP-ribosyl cysteine residues was studied in subcellular fractions of rat liver. Proteins modified on cysteine were detected only in the plasma membrane fraction. Pertussis toxin is known to disrupt signal transduction of ADP-ribosylation of cysteine residues of plasma membrane GTP binding proteins. The results described here raise the interesting possibility that the endogenous modification of plasma membrane protein cysteine residues may be involved in signal transduction.
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PMID:Modification of plasma membrane protein cysteine residues by ADP-ribose in vivo. 211 25

Endothelial cells release nitric oxide from L-arginine, and this pathway can be inhibited by the analogue of L-arginine, NG-monomethyl-L-arginine (L-NMMA). The effect of L-NMMA on endothelium-dependent relaxation of epicardial porcine coronary arteries was studied in isolated blood vessels suspended in organ chambers for isometric tension recording. Endothelium-dependent relaxations to bradykinin, serotonin, and the alpha 2-adrenergic agonist clonidine were evaluated in the presence and absence of L-NMMA (10(-5)-10(-3) M). L-NMMA, as well as the inhibitor of guanylate cyclase methylene blue (10(-5) M) and hemoglobin (10(-5) M), inhibited endothelium-dependent relaxation to serotonin and clonidine. The effect of L-NMMA could be reversed by L-arginine but not by D-arginine. In contrast, L-NMMA, methylene blue, and hemoglobin caused a weak inhibition of the endothelium-dependent relaxation evoked by bradykinin; indomethacin and tranylcypromine had no effect. The inhibitor of Gi proteins pertussis toxin (100 ng/ml) abolished the relaxations evoked by clonidine and markedly reduced those evoked by serotonin but did not affect those caused by bradykinin. In the presence of pertussis toxin, L-NMMA induced a further reduction of the relaxations to serotonin, suggesting that inhibition of Gi proteins does not completely prevent the activation of the L-arginine pathway. Thus endothelium-dependent relaxations to serotonin and to the alpha 2-adrenergic agonist clonidine are mediated through the release of nitric oxide formed from L-arginine in endothelial cells, whereas bradykinin evokes endothelium-dependent relaxations via a different pathway.
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PMID:Different activation of L-arginine pathway by bradykinin, serotonin, and clonidine in coronary arteries. 212 44

In rat myometrial membranes, two 3H-Bradykinin binding sites with KD values of 16 pM and 1.0 nM were identified. Employed at pM concentrations, bradykinin stimulated high affinity GTPases. This effect was abolished by the bradykinin antagonist, [D-Arg(Hyp3-Thi5,8, D-Phe7)]bradykinin (10 microM), and by treatment of membranes with pertussis toxin. Myometrial membranes contained two pertussis toxin substrates of 40 and 41 kDa, which corresponded immunologically to alpha-subunits of Gi-type G-proteins. The faster migrating substrate was tentatively identified as Gi2 alpha-subunit. The electrophoretic mobility of the slower migrating Gi alpha-subunit was very similar to that of the Gi3 alpha-subunit. Go alpha-subunits were not detected. Thus, in uterine smooth muscle, G-proteins of the Gi-family (Gi2, Gi3) couple high-affinity bradykinin receptors to their effector enzymes.
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PMID:A high-affinity bradykinin receptor in membranes from rat myometrium is coupled to pertussis toxin-sensitive G-proteins of the Gi family. 215 33

The murine BALB/c 3T3 fibroblast clone SV-T2 (3T3 cells) expresses receptors for the nonapeptide bradykinin. In these cells, bradykinin stimulates both inositol phosphate (InsP) formation and arachidonic acid release by independently activating phospholipase C and phospholipase A2, respectively. These actions of bradykinin are mediated by a receptor(s) coupled to pertussis toxin-insensitive guanine nucleotide-binding proteins. Bradykinin-stimulated increases in InsP lead to the mobilization of intracellular Ca2+. We examined the expression of 3T3 receptors for bradykinin in oocytes from Xenopus laevis, cells capable of in vitro expression of foreign mRNA for receptors coupled to the mobilization of Ca2+. Poly(A)+ mRNA was prepared from 3T3 cells and expression of receptors for bradykinin was demonstrated by agonist-mediated stimulation of 45Ca2+ efflux from oocytes injected with 50 ng of poly(A)+ RNA. Bradykinin-stimulated efflux of 45Ca2+ was dose dependent (EC50 = 15 nM) and blocked by the specific mixed B1,B2 bradykinin antagonist NPC 567 but not by the B1 antagonist desArg9[Leu8]bradykinin. Size fractionation of 3T3 poly(A)+ RNA on a sucrose gradient demonstrated a single peak of bradykinin-stimulated 45Ca2+ efflux, with an approximate mRNA size of 4.5 kilobases. Bradykinin-stimulated 45Ca2+ efflux in size-fractionated mRNA was clearly separable from response to [Arg]vasopressin at another receptor linked to InsP formation and Ca2+ mobilization in 3T3 cells.
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PMID:Functional expression of B2 bradykinin receptors from Balb/c cell mRNA in Xenopus oocytes. 216 13

Studies were performed to investigate regulatory pathways of loop diuretic-sensitive Na+/K+/Cl- cotransport in cultured rat glomerular mesangial cells. Angiotensin II, alpha-thrombin, and epidermal growth factor (EGF) all stimulated Na+/K+/Cl- cotransport in a concentration-dependent manner. Pertussis toxin pretreatment reduced the effects of angiotensin II and alpha-thrombin but not that of EGF. Addition of the protein kinase C inhibitor staurosporine or down-regulation of protein kinase C by prolonged incubation with phorbol 12-myristate 13-acetate partially reduced the effects of angiotensin II and alpha-thrombin and completely blunted the phorbol 12-myristate 13-acetate-induced stimulation of Na+/K+/Cl- cotransport but did not affect EGF-induced stimulation. Exposure of cells to a calcium ionophore, A23187, resulted in a concentration-dependent stimulation of Na+/K+/Cl- cotransport, which was not significantly inhibited by down-regulation of protein kinase C but was completely inhibited by the calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). Stimulation of the cotransport by angiotensin II or alpha-thrombin was also partially inhibited by W-7. Inhibitory effects of protein kinase C down-regulation and W-7 were additive and, when combined, produced a complete inhibition of angiotensin II-induced stimulation of Na+/K+/Cl- cotransport. In saponin-permeabilized mesangial cells, phosphorylation of a synthetic decapeptide substrate for Ca2+/calmodulin-dependent kinase II, Pro-Leu-Ser-Arg-Thr-Leu-Ser-Val-Ser-Ser-NH3, was demonstrated. Maximal activation of the decapeptide substrate phosphorylation required the presence of Ca2+ and calmodulin and was dependent on Ca2+ concentration. These findings indicate that stimulation of Na+/K+/Cl- cotransport by angiotensin II and alpha-thrombin is mediated by protein kinase C and Ca2+/calmodulin-dependent kinases whereas the action of EGF is mediated by other pathways.
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PMID:Agonist stimulation of Na+/K+/Cl- cotransport in rat glomerular mesangial cells. Evidence for protein kinase C-dependent and Ca2+/calmodulin-dependent pathways. 217 Mar 89

During the course of whooping cough, Bordetella pertussis interacts with alveolar macrophages and other leukocytes on the respiratory epithelium. We report here mechanisms by which these bacteria adhere to human macrophages in vitro. Whole bacteria adhere by means of two proteins, filamentous hemagglutinin (FHA) and pertussis toxin, either of which is sufficient to mediate adherence. FHA interacts with two classes of molecules on macrophages, galactose-containing glycoconjugates and the integrin CR3 (alpha M beta 2, CD11b/CD18). The interaction between CR3 and FHA involves recognition of the Arg-Gly-Asp (RGD) sequence at positions 1097-1099 in FHA. This study demonstrates that bacterial adherence can be based on the interaction of a bacterial adhesin RGD sequence with an integrin and that bacterial adhesins can have multiple binding sites characteristic of eukaryotic extracellular matrix proteins.
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PMID:Recognition of a bacterial adhesion by an integrin: macrophage CR3 (alpha M beta 2, CD11b/CD18) binds filamentous hemagglutinin of Bordetella pertussis. 236 31

Eosinophil granule major basic protein (MBP) is a 13,800 MW arginine-rich polypeptide that is unique among basic molecules in its ability to stimulate human basophil histamine release. We examined the Ca2+ requirements and pharmacological regulation of MBP-stimulated histamine release. Minimal MBP-induced histamine release occurred in the absence of extracellular Ca2+, whereas addition of 0.1 mM Ca2+ resulted in 70% of the maximum histamine release response. Maximum histamine release required 0.5 to 1 mM extracellular Ca2+. The MBP-induced histamine release was blocked by a calmodulin antagonist and by theophylline and was partially inhibited by an inhibitor of phospholipase A2. Release was unaffected by inhibition of protein kinase C. Basophil pretreatment with pertussis toxin also resulted in a concentration-dependent inhibition of release, suggesting involvement of a GTP regulatory protein in the activation mechanism. Histamine release stimulated by a 13,900 MW poly-L-arginine exhibited a dissimilar pharmacological profile from that of MBP. These results support the non-cytolytic nature of the MBP activation mechanism and identify pharmacological approaches for control of MBP-induced mediator release.
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PMID:Pharmacological control of human basophil histamine release stimulated by eosinophil granule major basic protein. 246 46

The functional development of the inhibitory guanine nucleotide-binding regulatory protein (Gi) and anti-diuretic hormone (ADH) activity was investigated in rat testes. Adult (90-day-old), adolescent (40-day-old), prepubertal (23-day-old), and fetal (20.5 days of gestation) testis cells were cultured with 100 ng/ml pertussis toxin for 24 h. The cells were then cultured with human chorionic gonadotropin (hCG), the ADH agonist arginine vasotocin (AVT), or a combination of the two. Testis cells from rats 23, 40, and 90 days of age that were incubated with hCG increased testosterone production when compared with controls. Preincubation of the cells from postnatal rats with pertussis toxin significantly increased hCG-stimulated testosterone secretion when compared to cells preincubated in medium only at all three ages. AVT suppressed hCG-stimulated testosterone secretion, but this suppression was partially reversed in cells from all postnatal ages preincubated with pertussis toxin. Fetal testis cells showed no response to preincubation with pertussis toxin, even when levels were increased to 400 ng/ml or when pertussis toxin treatment was continued throughout the culture period. AVT also had no effect on fetal testis cells. These results indicate that the Gi protein and AVT are not functional in fetal testes but are active from prepubertal stages of development through maturity.
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PMID:Development of the inhibitory guanine nucleotide-binding regulatory protein in the rat testis. 250 66


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