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)

Immunological properties of a low toxicity lipopolysaccharide (BP-LPS) extracted from Bordetella pertussis (Tohama strain) which was reported to have high antitumor activity against murine tumors were examined and compared with those of LPS extracted from other enterobacteria. The activation or stimulation of murine macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, BP-LPS was clearly less active in its stimulation of murine and human neutrophils as estimated by neutrophil-adherence assay and by their TNF production than E. coli LPS. Furthermore, BP-LPS also suppressed the activation of human neutrophils by Escherichia coli LPS. A comparative study with 7 LPS preparations indicated that their toxicity in terms of animal body weight loss correlated with their ability to induce human neutrophil adherence. The inability of BP-LPS to activate neutrophils may thus have some bearing on its low toxicity.
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PMID:Characterization of immunological activity of a low toxicity antitumor lipopolysaccharide from Bordetella pertussis. 785 14

Astrocytes, when appropriately stimulated, produce a variety of cytokines including TNF-alpha. Production of TNF-alpha by astrocytes stimulated with Newcastle disease virus (NDV) is achieved by transcriptional activation and mRNA stabilization. A PKC-dependent pathway is responsible for a 10-fold increase in TNF-alpha mRNA stability by reducing poly(A) tail removal. The present study examined signal pathways induced by NDV in primary rat astrocytes that are responsible for TNF-alpha gene transcription as well as the possible source of kinase activity required for mRNA stabilization. Transcription of TNF-alpha gene in astrocytes stimulated by NDV or LPS and IFN-gamma was inhibited completely by the tyrosine kinase inhibitor herbimycin, and partially by a PKC inhibitor H7, as determined by nuclear run-on assay. HA-1004, a cyclic nucleotide-dependent kinase inhibitor, showed no effect. These results indicated that tyrosine kinase signaling pathways seemed to precede the activation of PKC in induction of TNF-alpha gene. Increase in tyrosine kinase activity in NDV-infected astrocytes was demonstrated by a two- to threefold increase in tyrosine phosphorylation of Pl-PLC gamma 1. Because astrocytes contain minimal Pl-PLC beta, and NDV-induced TNF-alpha mRNA was affected by pertussis toxin only modestly, Pl-PLC gamma 1 is likely the enzyme responsible for DAG generation and the PKC-dependent mRNA stabilization in response to NDV.
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PMID:Tyrosine kinase activation by Newcastle disease virus is required for TNF-alpha gene induction in astrocytes. 808 95

A lipopolysaccharide (BP-LPS) isolated from killed Bordetella pertussis (Tohama strain) was determined to have low toxicity based on the mortality and decrease in body weight of BP-LPS-injected mice. BP-LPS, administered intradermally or intraperitoneally, clearly inhibited the growth of an MM46 murine mammary carcinoma. When compared with a toxic Escherichia coli-derived LPS, BP-LPS displayed excellent anti-tumour activity against MH134 hepatoma and Meth A fibrosarcoma. As part of a combined chemotherapy/immunotherapy regimen, BP-LPS also seemed to prolong the lifespan of mice inoculated with Lewis lung carcinoma. BP-LPS thus appears to have valuable characteristics as an anti-tumour agent.
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PMID:Anti-tumour activity of low-toxicity lipopolysaccharide of Bordetella pertussis. 819 67

The effect of the addition of (2,6-O-dimethyl)-beta-cyclodextrin (Me beta CD) during growth of Bordetella pertussis in synthetic Stainer-Scholte liquid medium (SS) on lipopolysaccharide (LPS; endotoxin) release was investigated. The Me beta CD concentration used (3 mg/ml) was chosen according to the optimal level found in previous studies to enhance major soluble antigen production. The profiles in SDS-PAGE (sodium dodecyl sulphate/polyacrylamide gel electrophoresis) of LPS extracted from cells grown in SS and SS + Me beta CD media revealed similar patterns. Although the LPS content of whole cells decreased during cell growth, yields obtained at different growth periods in cyclodextrin medium were lower than those corresponding to SS medium alone. Consequently, the level of LPS released in supernatants of both media increased during cellular growth. This amount of free LPS was higher in the cyclodextrin liquid medium and became significant at the beginning of the stationary growth phase. Binding of cyclodextrin to pertussis cells could account for the data obtained. Similar results were obtained with all species of the genus Bordetella.
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PMID:Release of lipopolysaccharide during Bordetella pertussis growth. 821 Jun 77

We have previously reported various inductive effects of nitric oxide on human PBMC. We describe a novel and potentially important mechanism of nitric oxide signaling-through direct activation of guanine nucleotide-binding proteins (G proteins). We have found that nitric oxide treatment of membranes isolated from fresh human PBMC enhances the ability of these membranes to hydrolyze [gamma-32P]GTP and bind [gamma-35S]GTP. In addition, treatment of whole cells with nitric oxide yielded membranes with enhanced GTPase activity. Furthermore, the GTPase activity of pure, recombinant Gs alpha, Gi alpha 1, and p21ras was greatly enhanced by nitric oxide. In support of the existence of this pathway in whole cells, we found that the G protein inhibitor, GDP-beta-S, blocked NF-kappa B translocation induced by nitric oxide or LPS in permeabilized cells. In addition, nitric oxide greatly reduced the pertussis toxin-mediated ADP-ribosylation of 45- and 41-kDa proteins in membranes of these cells. Because G proteins play a central role in many diverse signaling systems, activation by an endogenous and inducible oxidant may represent a novel signaling pathway.
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PMID:Nitric oxide signaling: a possible role for G proteins. 825 18

We have previously shown that minimally oxidized LDL (MM-LDL) activated endothelial cells to increase their interaction with monocytes but not neutrophils, inducing monocyte but not neutrophil binding and synthesis of monocyte chemotactic protein-1 and monocyte colony-stimulating factor (M-CSF). In the present studies we have examined the signaling pathways by which this monocyte-specific response is induced. Both induction of monocyte binding and mRNA levels for M-CSF by MM-LDL were not inhibited in protein kinase C-depleted endothelial cells. A number of our studies indicate that cAMP is the second messenger for the effects of MM-LDL cited above. Incubation of endothelial cells with MM-LDL caused a 173% increase in intracellular cAMP levels. Agents which increased cAMP levels, including cholera toxin, pertussis toxin, dibutyryl cAMP, and isoproterenol mimicked the actions of MM-LDL. Agents which elevated cAMP were also shown to activate NF kappa B, suggesting a role for this transcription factor in activation of monocyte-endothelial interactions. Although endothelial leukocyte adhesion molecule (ELAM) mRNA synthesis can be regulated by NF kappa B, ELAM was not expressed and ELAM mRNA was only slightly elevated in response to MM-LDL. We present evidence that induction of neutrophil binding by LPS is actually suppressed by agents that elevated cAMP levels.
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PMID:Minimally modified low density lipoprotein-induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate. 839 92

Using radioiodinated, photoactivable, reducible cross-linker conjugated bacterial endotoxic lipopolysaccharide (125I-ASD-LPS), we have demonstrated that LPS selectively binds to the S2 subunit of pertussis toxin (PT). Since LPS also interacts with the S2 subunit of the B-oligomer of the toxin, the binding of LPS to PT is not A-protomer (S1 subunit) dependent. The binding can be inhibited with native underivatized LPS and with purified lipid A, suggesting that the binding is mediated through the lipid A moiety of the LPS molecule. The binding of PT to LPS can be inhibited by bovine fetuin glycoprotein. Since PT has been demonstrated to interact specifically with N-linked oligosaccharide side chains of fetuin, the interaction of LPS with the S2 subunit of PT may involve carbohydrate-dependent interactions of the disaccharide backbone of lipid A with S2. Additional studies have documented that LPS binding to PT may be competitively inhibited by lysozyme but not by polymyxin B. Sequence analysis has allowed identification of a high degree of amino acid sequence similarity between the S2 subunit of PT and hen egg white lysozyme at the N-terminal 80-residue regions. Shared N-terminal sequence similarity between lysozyme, PT-S2, and a third LPS-binding protein alpha-lactalbumin allows tentative identification of a second family of LPS binding proteins.
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PMID:Lipopolysaccharide interaction with S2 subunit of pertussis toxin. 841 48

It has been established that LPS, the major constituent of the outer membrane of gram negative bacteria, stimulates macrophages to produce numerous inflammatory mediators, including TNF-alpha and nitric oxide (NO). Both TNF-alpha and NO are important in the macrophage-mediated cytotoxicity against invading microorganisms and tumor cells. Although many LPS-dependent immune responses have been well characterized phenomenologically, the precise signal transduction pathways in LPS-induced macrophage activation are not clear. We reported that 1) pretreatment of C3HeB/FeJ mouse peritoneal macrophages with pertussis toxin (PT) markedly enhanced LPS-induced TNF-alpha production but inhibited LPS-dependent NO production under the same conditions; 2) kinetics of the PT effects on these LPS-responses were correlated with PT-mediated ADP-ribosylation of a 41-kDa protein(s); and 3) PT pretreatment did not correct the refractory states of C3H/HeJ macrophages to wild type smooth-LPS. These results suggest that LPS stimulates TNF-alpha and NO production in mouse peritoneal macrophages through different biochemical pathways, and that the signal transduction for both pathways is regulated by a PT-sensitive factor. It is possible that this factor is a guanine nucleotide-binding regulatory protein(s). Finally our data indicate that it is unlikely that the defect of the C3H/HeJ macrophages in response to LPS is at the level of this PT-sensitive factor.
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PMID:Pertussis toxin-sensitive factor differentially regulates lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production in mouse peritoneal macrophages. 842 28

During endotoxin shock macrophages produce arachidonic acid (AA) metabolites, nitric oxide (NO) and interleukin 6 (IL-6). In contrast, macrophages from endotoxin tolerant rats become hyporesponsive to LPS-induced AA metabolites production. However the role of NO and IL-6 during endotoxin tolerance is not known. Therefore, we evaluated the production of the AA metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), IL-6 and NO (by nitrite measurement) by peritoneal macrophages from endotoxin tolerant rats. Since pertussis toxin (PT) sensitive guanine nucleotide binding regulatory (Gi) protein activity is altered during endotoxin tolerance, we also studied the effect of PT on the regulation of the above mediators synthesis. Endotoxin tolerance was induced in rats by intraperitoneal injection of a sublethal dose of Salmonella enteritidis lipopolysaccharide (LPS, 100 micrograms/kg ip). Peritoneal macrophages were harvested 24 hours after LPS injection and stimulated in vitro with LPS (50 micrograms/ml) for determination of NO activity by nitrite, 6-keto-PGF1 alpha and IL-6 production. In macrophages collected from vehicle-pretreated rats (control) LPS stimulates all three mediators. In vivo pretreatment with LPS induced a desensitization of macrophages to LPS-induced 6-keto-PGF1 alpha production compared to control macrophages (p < 0.001). LPS-stimulated IL-6 synthesis was also partially, but not completely, reduced in tolerant macrophages (p < 0.001 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reorientation of macrophage mediator production in endotoxin tolerance. 852 61

Following the demonstration of the strong adjuvant effect of whole-cell DTP vaccine (wDTP) on the immune responses to influenza subunit vaccine, studies were undertaken to identify the component of wDTP responsible for the adjuvant effect, and to determine if acellular DTP (aDTP) vaccine was as effective since it is less reactogenic and likely to replace wDTP for primary or secondary immunisation. In addition, wDTP and aDTP were directly compared in a dose-response study. Experiments in mice indicated that the adjuvant effect of wDTP resided in the LPS component of B. pertussis, since purified LPS enhanced the IgG antibody response, the IgG subclass response and protection to the same level as wDTP. An adjuvant effect was detected using aDTP, but was statistically less pronounced than wDTP by a factor of some 100-fold. These results suggest that immunisation against influenza in infants and young children can be achieved combining small amounts of influenza antigen with wDTP or LPS, and to a lesser extent by combining vaccine with aDTP. However, these results were obtained in mice and should be confirmed in man since species vary considerably in response to adjuvant.
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PMID:Immune response and protection against influenza A infection in mice immunised with subunit influenza A vaccine in combination with whole cell or acellular DTP vaccine. 857 39


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