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)

Previously, we identified peptides that stimulate phosphoinositide hydrolysis in several leukocyte cell lines from mixtures of random hexapeptide sequences. Moreover, the peptides activate phospholipase C via a pertussis toxin-sensitive G protein-coupled receptor. We now investigate the structure-activity relationship of the peptides with the goal of improving the activity of the peptides, as well as the biologic function of the peptides. Substitution of the L-methionine at the C terminus of peptides with D-methionine markedly increased the effectiveness of the peptides. The half-maximal effective concentrations of MKYMPm-NH2 and WKYMVm-NH2 for stimulation of phosphoinositide hydrolysis in U266 cells were 30 and 0.5 nM, respectively. By BIAcore analysis we confirmed the existence of a receptor for WKYMVm-NH2. Furthermore, the intracellular calcium concentration increase induced by WKYMVm-NH2 was not inhibited by several chemoattractants (FMLP, IL-8, platelet-activating factor, C5a, granulocyte-macrophage CSF, and granulocyte CSF) suggests that WKYMVm-NH2 has a unique cell surface receptor on leukocytes. WKYMVm-NH2 stimulated the phosphoinositide hydrolysis in U937, HL60, and U266 cells, as well as in human neutrophils. Moreover, WKYMVm-NH2 is more effective than FMLP in the production of superoxide in human neutrophils. The data suggest that WKYMVm-NH2 may have the ability to activate the microbicidal functions of human neutrophils.
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PMID:A peptide with unique receptor specificity: stimulation of phosphoinositide hydrolysis and induction of superoxide generation in human neutrophils. 902 31

The stimulation of granulocyte macrophage-colony stimulating factor (GM-CSF) by interleukin-1 (IL-1) has been shown to be counteracted in different mesenchymal cell systems by cyclic adenosine monophosphate (cAMP) agonists. The aim of this study was the evaluation of different cAMP agonists on GM-CSF expression in human bone marrow stromal cells. Incubation of secondary haematopoietic progenitor cell deprived human stromal cell cultures with IL-1 or TNF-alpha induced GM-CSF protein expression in culture supernatants and GM-CSF-mRNA in adherent stromal cells. The coincubation with 8-bromo-cAMP (8BrcAMP), a water soluble cAMP analogue, inhibited this GM-CSF stimulation at the protein and the mRNA level. This effect was dose dependent with a maximal inhibition of about 65% occurring at a 8BrcAMP concentration of 0.75 mM. In addition to 8BrcAMP, other cAMP agonists such as dibutyryl-cAMP, forskolin, pertussis toxin, or prostaglandin E2 (PGE2) had the same inhibitory effect on GM-CSF stimulation by IL-1. Coincubation with the cyclooxygenase inhibitor indomethacin had no significant influence on GM-CSF expression in stromal cells. Our results provide evidence that the previously described inhibitory effect of cAMP agonist PGE2 on haematopoietic progenitor cells in vivo is, at least in part, mediated by modulating the expression of GM-CSF in bone marrow stromal cells.
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PMID:cAMP analogues downregulate the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in human bone marrow stromal cells in vitro. 970 7

The lipid antigens used in the Bordet-Wassermann and prepared by Landsteiner and Marie for syphilis tests from 1909 to 1949 were non specific but have certain common features with the spirochete body. For more than forty years the Bordet-Wassermann reaction, associated with flocculation (Kahn) or agglutination (Kline-VDRL) was used to detect cases of tremonematosis despite frequent false positives reactions due to other infections. In 1949, the Nelson and Mayer test was introduced. This test was based on a rigorously specific reaction based on an antigen of live virulent Treponema pallidum. Culture being impossible, the strain had to be, and still is, maintained by weekly passage on rabbit testicles. These manipulations are very dangerous and the technique is difficult, being performed only in specialized laboratories. This test however made it possible to identify the specificity of lipid tests and led to the development of specific immunofluorescent reactions (FTA) in 1959 and of hemagglutination test (TPHA) in 1969. In 1980, we introduced a simple treponemic reaction (FTA or TPHA) associated with a lipid reaction (VDRL) for screening. The specificity of these tests is not however perfect and the Nelson test remains useful as a highly specific reaction. A simple test with comparable specificity was long awaited and is now available with immunoblotting as for HIV, boreliosis and pertussis, etc. We propose this new reaction to replace the Nelson test because it is specific, is sensitive early, distinguishes between IgG and IgM and is not dangerous to manipulate. We have tested it in over one hundred selected sera of CSF from subjects with recent, former or nervous syphilis as well as cases susceptible of producing false positive reactions and have concluded that immunoblotting is highly specific and sensitive. We recommend official approval of this test to replace the Nelson test.
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PMID:[Immunoblotting for the serodiagnosis of syphilis. A candidate to replace the Nelson-Mayer test]. 1007 52

We have used the Stamper-Woodruff frozen-section assay (FSA) to characterize the integrin and activation steps involved in adhesion of peripheral blood eosinophils and neutrophils to nasal polyp endothelium (NPE). Eosinophil and neutrophil adhesion was significantly inhibited by monoclonal antibodies (mAbs) against CD18 (beta2) and CD11a-c. Eosinophil adhesion was also inhibited to a lesser extent by mAbs against CD29 (beta1), CD49d (alpha4), and vascular cell adhesion molecule-1. The involvement of integrins raised the possibility of an activation step being involved in the adhesion process. Although stimulation of the cells with granulocyte macrophage colony-stimulating factor (GM-CSF) before the assay failed to modulate adhesion, binding was inhibited by up to 50% by treatment of the leukocytes with azide. In addition, neutrophil adhesion was completely abrogated by pertussis toxin (PT) and inhibited by about 50% by the platelet-activating factor antagonist WEB 2086 and antibodies against interleukin (IL)-8 and the two IL-8 receptors IL8RA and IL8RB (C-X-CR1 and -CR2). In contrast, eosinophil adhesion was unaffected by PT, WEB 2086, or anti-IL8R mAbs. mAbs against CCR-3, IL-3, IL-5, and GM-CSF also had no effect. This study demonstrates that eosinophil and neutrophil adhesion to NPE in the FSA conforms to the multistep paradigm for leukocyte adhesion and can be used to model the molecular basis for adhesion to endothelium in the context of chronic inflammatory disease. Using this assay, we have observed significant differences in integrin usage between eosinophils and neutrophils and a striking difference in the mechanism of integrin activation. These differences could explain, in part, the preferential accumulation of eosinophils in diseases such as asthma.
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PMID:Characterization of the integrin and activation steps mediating human eosinophil and neutrophil adhesion to chronically inflamed airway endothelium. 1034 Sep 44

In mice whose Gi/o-protein function had been impaired by antisense 'knock-down' or pertussis toxin treatment, i.c.v. injection of myr+-Gi/o alpha subunits restored the effectiveness of beta-endorphin, morphine, DPDPE, clonidine and neurotensin to produce antinociception. Myr+-G alpha subunits of the class of G-proteins actually impaired were more effective than unlike but related myr+-G alpha subunits. Selectivity was noted in that only exogenous myr+-G alpha subunits affected (enhanced) the activity of agonists in G alpha-deficient signalling systems. This treatment had little effect on agonist potency when the impairment resided at the receptor level. The potential of the opioids, clonidine and R-PIA to increase G alpha-related in vitro hydrolysis of GTP was also re-established after injecting myr+-Gi2 alpha subunits into Gi2-knocked-down mice. Myr+-Gi2 alpha subunits pre-incubated with GTPgammaS or GDPbetaS before i.c.v. injection did not improve the activity of agonists in vivo (antinociception) or in vitro (regulation of low Km GTPase). After impairing the function of PKCbeta1 by antisense treatment or with the inhibitor H7, the effect of myr+-G alpha subunits on agonist potency was prevented. Electron microscope analysis showed the entry of gold-conjugated myr+-G alpha subunits into neural cells. These particles were found in the cytoplasm, associated with the plasma membranes of different neuronal processes and also in synaptic junctions. In cultured neurons and astrocytes myr+-Gi2 alpha-associated fluorescence was internalised in a dose-dependent manner and distributed in the plasma membrane and cytosol, as well as in nuclei of dividing astrocytes. Thus, G alpha subunits in CSF enter into neurons and functionally couple to the receptor-triggered signalling cascade. As G-proteins have been implicated in the pathophysiology of several neural disorders, this finding may be valuable in the therapy of such dysfunctions.
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PMID:Myr+-Gi2 alpha and Go alpha subunits restore the efficacy of opioids, clonidine and neurotensin giving rise to antinociception in G-protein knock-down mice. 1060 81

Like opioid tolerance, neuropathic pain syndrome manifested by hyperalgesia and allodynia responds poorly to opioids. Hitherto, its development is still not clear and its treatment and prevention are still disputable. Pertussis toxin (PTX) which ADP-ribosylates the alpha-subunit of inhibitory guanine nucleotide binding regulatory proteins (Gi/Go), is used to induce morphine tolerance through intrathecal (i.t.) injection. It decreases the antinociceptive effect of opioid receptor agonists, and produces a thermal hyperalgesia as well. With treatment of PTX the inhibitory Gi- and Go-proteins signal transduction is inactivated. Inhibition of the inhibitory system would likely lead to a predominance of the excitatory system. Intrathecal PTX administration has also been suggested as a model for study of the central mechanisms of neuropathic pain. In our previous studies, with intrathecal microdialysis and drug delivery techniques, we correlated the biochemical and pharmacological effects on the behavioral expressions of i.t. PTX-treated rats. Intrathecal PTX administration would induce thermal hyperalgesia in rats, with accompaniments of a prolonged increase in the concentrations of excitatory amino acids (EAAs), glutamate and aspartate, and a decrease in the concentration of the inhibitory amino acid (IAA) glycine in the spinal CSF dialysates. The PTX-induced thermal hyperalgesia peaked between day 2 and 4, but no cold allodynia is observed; i.t. administration of N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosponovaleric acid (D-AP5), glycine and protein kinase C (PKC) inhibitor chelerythrine attenuated the thermal hyperalgesia. The PKC gamma content of both synaptosomal and cytosolic fractions were significantly increased in PTX-treated rats. In contrast, the levels of PKC alpha, beta I, or beta II isozymes in these fractions were unaffected. Infusion of NMDA antagonist D-AP5 prevented both the thermal hyperalgesia and the increase in PKC gamma expression in PTX-treated rats. Similar to our previous report, i.t. PTX reduced morphine's analgesic effect. PKC inhibitor chelerythrine attenuated this reduction of morphine's analgesia, and an inhibition of the morphine-evoked EAAs release was observed in PTX-treated rats as well. Taken together, i.t. PTX-induced neuropathic pain syndrome is accompanied by increasing of EAAs, decreasing of IAA release, and a selective increasing of PKC gamma expression in the spinal cord. Inhibition of PKC not only blocked thermal hyperalgesia, but also reversed the reduction of morphine's analgesic effect in PTX-rats. These results suggest that PTX-induced neuropathic pain syndromes are involved in EAAs, IAAs and PKC alternations.
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PMID:Implications of intrathecal pertussis toxin animal model on the cellular mechanisms of neuropathic pain syndrome. 1476 16

A recombinant pertussis DNA vaccine was described here with its immunogenicity and the ability to induce protection against B. pertussis infection in mice. Three immunodominant antigen gene fragments of pertussis, pertussis toxin subunit 1 (pts1), fragments of pertactin (prn) and filamentous hemagglutinin (fha), were recombined as fragment pts1-prn-fha named ppf, and it was cloned to plasmid pVAX1 as pVAX1/ppf. Compared to those injected with pVAX1, the mice injected with pVAX1/ppf significantly elicited more antigen specific antibody anti-PTS1, anti-PRN, anti-FHA and cytokine IL-10, IFN-gamma. When pGM-CSF was coinjected with pVAX1/ppf, the mice showed significantly increases of the three antibodies and cytokine IL-10, IL-4, IFN-gamma and TNF-alpha compared to those injected with pVAX1 only. The mice in group pVAX1/ppf & pGM-CSF, in particular; induced much more anti-PTS1, IL-4 and TNF-alpha than those in group pVAX1/ppf. In the intracerebral mouse protection test, the mice immunized with pVAX1/ppf or pVAX1/ppf & pGM-CSF induced protection to a lethal dose of B. pertussis. The results indicate that recombinant DNA vaccine and pGM-CSF coinjection can induce protective immunity against B. pertussis, demonstrating a valuable method to prevent pertussis.
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PMID:Protective immunity against Bordetella pertussis by a recombinant DNA vaccine and the effect of coinjection with a granulocyte-macrophage colony stimulating factor gene. 1717 60

The aim of the present study was to examine the effect of ultra-low-dose naloxone on pertussis toxin (PTX)-induced thermal hyperalgesia in rats and its underlying mechanisms. Male Wistar rats, implanted with an intrathecal catheter with or without a microdialysis probe, received a single intrathecal injection of PTX (1 microg in 5 microl saline). Four days after PTX injection, they were randomly given a different dose of naloxone (either 15 microg or 15 ng in 5 microl saline), followed by a morphine injection (10 microg in 5 microl saline) after 30 min. The results found that PTX injection induced thermal hyperalgesia and increasing excitatory amino acid (EAA; L-glutamate and L-aspartate) concentration in the spinal CSF dialysates. Ultra-low-dose naloxone not only preserved the antinociceptive effect of morphine but also suppressed the PTX-evoked EAA release as well. Moreover, ultra-low-dose naloxone plus morphine administration inhibited the downregulation of L-glutamate transporters (GTs) and the L-glutamate-metabolizing enzyme glutamine synthetase (GS), and, moreover, inhibited microglial activation and suppressed cytokine expression in PTX-treated rat spinal cords. These results show that ultra-low-dose naloxone preserves the antinociceptive effect of morphine in PTX-treated rats. The mechanisms include (a) inhibition of pro-inflammatory cytokine expression, (b) attenuation of PTX-evoked EAA release, and (c) reversion of the downregulation of GT expression.
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PMID:Ultra-low-dose naloxone restores the antinociceptive effect of morphine and suppresses spinal neuroinflammation in PTX-treated rats. 1821 75

In humans, 10(11) neutrophils are released from the bone marrow per day, and these cells have a half-life in the blood of only approximately 6.5 h. Although it is generally believed that neutrophils are cleared from the circulation via the liver and spleen, in this study using (111)In-labeled senescent neutrophils, we show that in mice, 32% of neutrophils are cleared from the circulation via the bone marrow. We have previously shown that senescent neutrophils home to the bone marrow in a CXCR4-dependent manner, and we show here that pretreatment of neutrophils with pertussis toxin significantly inhibits neutrophil clearance via the bone marrow (75%), consistent with a role for chemokines in this process. By labeling senescent neutrophils with inert fluorescent microspheres, we have tracked their fate and shown that in vivo, they are ultimately phagocytosed by bone marrow stromal macrophages. Finally, we show that under noninflammatory conditions, circulating levels of neutrophils are regulated by granulocyte-colony stimulating factor (G-CSF), but not interleukin-17. Interestingly, we report that the uptake of apoptotic neutrophils by bone marrow macrophages stimulates their production of G-CSF in vitro. Taken together, these data provide evidence that the bone marrow represents a major site of neutrophil clearance in mice.
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PMID:The role of the bone marrow in neutrophil clearance under homeostatic conditions in the mouse. 1850 99

This study was designed to investigate the effect of acute intrathecal (i.t.) injection of amitriptyline (AMI) on the antinociceptive effect of morphine in rats treated with pertussis toxin (PTX). Male Wistar rats were implanted with an i.t. catheter for drug injection and some were implanted with an additional microdialysis probe used for CSF dialysate collection and measurement of excitatory amino acids (EAAs). The expression of glutamate transporters (GTs) in the spinal cord dorsal horn was also measured. A tail-flick test was performed and CSF dialysate was collected as the baseline-B value (day 0) before PTX (1 microg, i.t.) injection and at 4 days after PTX injection, but before drug challenge as the baseline-P value (day 4), and at 30, 60, 90, and 120 min after drug challenge on day 4. The baseline-P tail-flick latencies were significantly lower than the baseline-B values. In PTX-treated rats (day 4), morphine (10 microg, i.t.) did not produce an antinociceptive effect, but this was retained by acute AMI (15 microg, i.t.) pretreatment 30 min before morphine injection. In addition, concentrations of glutamate and aspartate were higher in baseline-P dialysates than in baseline-B dialysates, and the expression of the GTs (GLT-1, GLAST, and EAAC1) was downregulated by PTX treatment. Acute injection of PTX-treated rats with either AMI (15 microg, i.t.) or morphine (10 microg, i.t.) alone had no significant effect on CSF EAA concentrations and GT expression. In contrast, AMI (15 microg, i.t.) pretreatment followed 30 min later by morphine (10 microg, i.t.) injection inhibited the increase in EAA concentrations and reversed the downregulation of all three GTs. Our results show that AMI preserves the antinociceptive effect of morphine in PTX-treated rats. The mechanisms involve suppression of the increase in EAA concentrations in spinal CSF dialysates and reversion of GT expression in PTX-treated rats.
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PMID:Amitriptyline pretreatment preserves the antinociceptive effect of morphine in pertussis toxin-treated rats by lowering CSF excitatory amino acid concentrations and reversing the downregulation of glutamate transporters. 1868 Jul 32

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