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

Live vaccine vectors are usually very effective and generally elicit immune responses of higher magnitude and longer duration than nonliving vectors. Consequently, much attention has been turned to the engineering of oral pathogens for the delivery of foreign antigens to the gut-associated lymphoid tissues. However, no bacterial vector has yet been designed to specifically take advantage of the nasal route of mucosal vaccination. Herein we describe a genetic system for the expression of heterologous antigens fused to the filamentous hemagglutinin (FHA) in Bordetella pertussis. The Schistosoma mansoni glutathione S-transferase (Sm28GST) fused to FHA was detected at the cell surface and in the culture supernatants of recombinant B. pertussis. The mouse colonization capacity and autoagglutination of the recombinant microorganism were indistinguishable from those of the wild-type strain. In addition, and in contrast to the wild-type strain, a single intranasal administration of the recombinant strain induced both IgA and IgG antibodies against Sm28GST and against FHA in the bronchoalveolar lavage fluids. No anti-Sm28GST antibodies were detected in the serum, strongly suggesting that the observed immune response was of mucosal origin. This demonstrates, to our knowledge, for the first time that recombinant respiratory pathogens can induce mucosal immune responses against heterologous antigens, and this may constitute a first step toward the development of combined live vaccines administrable via the respiratory route.
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PMID:Induction of mucosal immune responses against a heterologous antigen fused to filamentous hemagglutinin after intranasal immunization with recombinant Bordetella pertussis. 875 82

An immunoregulatory role for vasoactive intestinal peptide (VIP) is suggested by the high concentrations in subsets of neurons supplying lymphoid organs and by the capacity of VIP to affect T lymphocyte functions. The Tsup-1 line of human T lymphoblastoma cells expresses both type I and type II G protein-coupled VIP receptors (Rs), as shown by detection of the encoding mRNAs with reverse transcription-polymerase chain reaction analyses. Northern blot quantification of the relative amounts of mRNA encoding the two VIPRs in Tsup-1 cells indicated that type II predominates over type I, as it does in human blood CD4+ T cells. Tsup-1 cells bound 125I-VIP to 8.95 x 10(4) high-affinity sites/cell (Kd = 6.0 nM) and 7.45 x 10(5) low-affinity sites/cell (Kd = 210 nM). VIP increased [cAMP]i in Tsup-1 cells (EC50 = 14.4 nM) and stimulated a rapid and transient increase in [Ca2+]i (EC50 = 30 nM). Functional coupling of G proteins to type II VIPRs was suggested by the change in binding of 125I-VIP to Tsup-1 cell membranes from two sites with Kd values of 3.8 and 109 nM to one site of Kd 30 nM by GTP-gamma-S and the suppression by pertussis toxin of increases in [Ca2+]i evoked by VIP. The VIP antagonists, VIP4-28 and (4-Cl-D-Phe6-Leu17) VIP, inhibited 125I-VIP binding by type II VIPRs, as well as VIP-elicited increases in [Ca2+]i and [cAMP]i. Type II VIPRs thus are the major transducers of VIP signals to a subset of human T cells.
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PMID:Predominant expression of type II vasoactive intestinal peptide receptors by human T lymphoblastoma cells: transduction of both Ca2+ and cyclic AMP signals. 892 82

Pertussis toxin from the gram-negative bacterium Bordetella pertussis is an ADP-ribosylase that modifies Gi proteins in mammalian lymphocytes and inhibits their capacity to traffic from blood into lymphoid tissues. We used this compound to induce lymphocytosis in rhesus macaques and to study its effects on SIV infection. Pertussis toxin injected at 25 micrograms/kg induced a transient lymphocytosis that peaked 3-8 days after administration and caused a rapid, transient decrease in the frequency of infectious cells in blood as judged by in vitro virus isolation assays. Lymphocyte subsets were altered during the lymphocytosis interval and sustained changes in CD8+ T cell levels were noted as long as 53 days after pertussis toxin injection. In situ hybridization studies showed that pertussis toxin altered the distribution of viral RNA in lymph nodes during the interval of lymphocytosis, and caused long-term changes with decreased virus replication in some tissue specimens.
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PMID:The lymphocytosis-promoting agent pertussis toxin affects virus burden and lymphocyte distribution in the SIV-infected rhesus macaque. 898 31

Hematopoietic progenitor cells migrate in vitro and in vivo towards a gradient of the chemotactic factor stromal cell-derived factor-1 (SDF-1) produced by stromal cells. This is the first chemoattractant reported for human CD34+ progenitor cells. Concentrations of SDF-1 that elicit chemotaxis also induce a transient elevation of cytoplasmic calcium in CD34+ cells. SDF-1-induced chemotaxis is inhibited by pertussis toxin, suggesting that its signaling in CD34+ cells is mediated by seven transmembrane receptors coupled to Gi proteins. CD34+ cells migrating to SDF-1 include cells with a more primitive (CD34+/CD38- or CD34+/DR-) phenotype as well as CD34+ cells phenotypically committed to the erythroid, lymphoid and myeloid lineages, including functional BFU-E, CFU-GM, and CFU-MIX progenitors. Chemotaxis of CD34+ cells in response to SDF-1 is increased by IL-3 in vitro and is lower in CD34+ progenitors from peripheral blood than in CD34+ progenitors from bone marrow, suggesting that an altered response to SDF-1 may be associated with CD34 progenitor mobilization.
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PMID:The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. 899 47

One of the current goals in vaccine development is the noninvasive administration of protective antigens via mucosal surfaces. In this context, the gut-associated lymphoid tissues have already been extensively explored. Vaccination via the nasal route has only recently been the focus of intensive investigation, and no live vector specifically designed for the respiratory mucosa is yet available. In this study we show that intranasal administration of the recombinant Bordetella pertussis BPGR60, producing the Schistosoma mansoni 28-kDa glutathione S-transferase (Sm28GST) protective antigen fused to filamentous hemagglutinin, induces priming in mice for the production of serum antibodies. In addition to significant levels of anti-Sm28GST immunoglobulin A (IgA) antibodies, high levels of anti-Sm28GST serum antibodies were obtained after intranasal boost with the purified antigen or infection with S. mansoni following intranasal priming with BPGR60. These antibodies were of the IgG1, IgG2a, and IgG2b isotypes, suggesting a mixed immune response. No priming was observed in animals that had received nonrecombinant B. pertussis or purified Sm28GST, indicating specific priming by BPGR60. This priming was also evident in immune protection against S. mansoni challenge. Significant protection against worm burden and egg output was obtained in mice primed with BPGR60 and intranasally boosted with purified Sm28GST. A lower but still significant degree of protection against egg output was also obtained in mice infected with a single dose of BPGR60. These results indicate that intranasal administration of recombinant B. pertussis can prime for serum antibody responses against a foreign antigen and for heterologous protection.
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PMID:Intranasal priming with recombinant Bordetella pertussis for the induction of a systemic immune response against a heterologous antigen. 900 11

Pertussis toxin (PT), produced by the causative agent of whooping cough, Bordetella pertussis, contributes to the immune dysfunction seen in infected patients. Treatment of laboratory animals with purified toxin reproduces many of the biological effects exhibited in the disease state, which include lymphocytosis, adjuvant effects for IgE secretion and delayed-type hypersensitivity reactions. In previous studies, we have demonstrated that PT pretreatment of intravenously transferred lymphocytes not only results in them being held up in the blood, but also causes a profound alteration in their positioning within the spleen. Pertussis toxin pretreated lymphocytes fail to traverse the layer of marginal zone macrophages encircling the white pulp, resulting in their exclusion from the lymphoid area of the spleen. Using a novel flow cytometric assay of cell division, the studies presented here show that a significant proportion of B, but not T, lymphocytes underwent proliferation after intravenous transfer of donor splenic lymphocytes to syngeneic recipients. This proliferation was markedly reduced by PT pretreatment of lymphocytes before transfer. In contrast, the in vitro proliferative responses of B lymphocytes to anti-IgM, LPS and antibody engagement of CD40 were unimpaired by exposure to the same levels of PT. Furthermore, the rate of in vivo decay of transferred B cells was accelerated by pretreatment with PT. Together, these data suggest PT impairs the receipt of signals which promote survival and proliferation of B cells, due to altered recirculation and positioning of lymphocytes.
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PMID:Pertussis toxin pretreatment alters the in vivo cell division behaviour and survival of B lymphocytes after intravenous transfer. 904 28

We describe a new method based on radioactive metabolic labeling with [3H]glycerol to study the lymphocyte trafficking in mice. Lymphocyte labeling with [3H]glycerol is time- and dose-dependent. Radioactive leaking is less significant than in 51Cr-labeled cells. Lymphocytes, labeled with [3H]glycerol, with 51Cr, or with both labels together show the same pattern of homing to Peyer's patches (PP), peripheral and mesenteric lymph nodes and spleen and homing shows the expected dependence on pertussis toxin (PTX)-sensitive signaling, suggesting that the labeling procedure with [3H]glycerol does not affect lymphocyte trafficking properties. Tissue accumulation can be readily assessed by scintillation counting of sonicated samples obtained after perfusion of the vasculature with saline to remove blood. Moreover, we show that cell labeling with [3H]glycerol provides improved sensitivity in assessing the accumulation of small numbers of labeled cells in non-lymphoid organs, and permits identification of homed leukocytes in histologic sections.
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PMID:Novel method for following lymphocyte traffic in mice using [3H]glycerol labeling. 913 28

The selectin adhesion molecules and chemoattractant receptors synergistically regulate leukocyte migration into lymphoid tissues and sites of inflammation, but little is known about how these families of receptors modulate each other's function. In this study, L-selectin was found to be phosphorylated in lymphoblastoid cell lines, and phosphorylation was enhanced by phorbol ester (phorbol 12-myristate 13-acetate (PMA)) treatment. Interactions between L-selectin and chemoattractant receptors were therefore examined using transfected rat basophilic leukemia cell lines (RBL-2H3) that expressed human L-selectin along with human leukocyte chemoattractant receptors. L-selectin was rapidly phosphorylated in cells treated with chemoattractants, thrombin, IgE receptor agonists, or PMA. Pertussis toxin or the protein kinase C inhibitor, staurosporine, completely blocked chemoattractant receptor-induced phosphorylation of L-selectin. PMA-induced phosphorylation was on serine residues within the cytoplasmic tail of L-selectin that have been well conserved during recent evolution. Although L-selectin phosphorylation was not essential for basal levels of adhesion through L-selectin in transformed cell lines, the rapid increase in ligand binding activity of L-selectin that occurs following leukocyte activation was blocked by staurosporine. These results demonstrate that L-selectin can be phosphorylated following engagement of chemoattractant receptors and suggest that this may be a physiologically relevant mechanism for the synergistic regulation of these receptors during leukocyte migration.
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PMID:Chemoattractant receptor-induced phosphorylation of L-selectin. 915 59

Lymph nodes and other solid tissues of the immune system are the principal sites for antigen presentation and lymphocyte activation. Lymphocytes in peripheral blood recognize the high endothelial venules within lymphoid tissues and cross from blood to tissue by the process of extravasation. Pertussis toxin is known to block extravasation and cause lymphocytosis in murine models but has not been studied extensively in nonhuman primates. We used intravenous injection of soluble pertussis toxin to induce a transient lymphocytosis in rhesus monkeys. The increase in total white blood cells was proportionally greater for lymphocytes than for polymorphonuclear cells and the CD4+ lymphocyte subpopulation increased more than the CD8+ cell population. The presence of immature polymorphonuclear cells suggested some activation of bone marrow. Clinical chemistry studies revealed an effect of pertussis toxin on liver function. Pertussis toxin is a powerful immunomodulatory agent that can disrupt and reorganize solid lymphoid tissues.
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PMID:Pertussis toxin induces lymphocytosis in rhesus macaques. 921 21

Previous results have shown that pertussis toxin-sensitive Gi proteins are likely to be involved in regulating the emigration of mature thymocytes from the thymus. In this study, a low stringency polymerase chain reaction (PCR) approach was used to identify Gi protein-coupled cell surface receptors expressed in mouse thymocytes. Among the ten G protein-coupled receptor cDNA isolated, the most prevalent cDNA encoded a polypeptide highly homologous to the human leukocyte-expressed seven-transmembrane-domain receptor LESTR, also referred to as HIV entry cofactor, fusin, or CXCR4. Isolation of full-length cDNA revealed that alternative RNA splicing produces transcripts encoding two isoforms of the murine LESTR, differing by the presence of two amino acids in the N-terminal portion of the longer protein. Functional reconstitution of recombinant murine LESTR with recombinant heterotrimeric G proteins in baculovirus-infected insect cells showed that both receptor variants mediate stromal cell-derived factor 1alpha activation of the pertussis toxin-sensitive G protein Gi2. Receptor subtype-specific reverse transcriptase-PCR analysis revealed differential expression of the two receptor mRNA in lymphoid tissues and brain, indicating that distinct functions are mediated by the two receptor isoforms in these tissues. The presence of LESTR mRNA in very early thymocytes as well as in immature (CD4+ CD8+) thymocytes suggests that both CD4 and LESTR are co-expressed and render developing human thymocytes susceptible for HIV entry, which may affect generation of both CD4+ CD8- and CD4- CD8+ mature lineages.
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PMID:Two murine homologues of the human chemokine receptor CXCR4 mediating stromal cell-derived factor 1alpha activation of Gi2 are differentially expressed in vivo. 929 51


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