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)

Human recombinant interleukin-2 and rat recombinant IL-2 microinjected into the locus coeruleus of rats, induced typical dose-dependent behavioural sedation and/or sleep and electrocortical synchronization. During sleep induced by this lymphokine a dose-dependent increase in total voltage power (0.25-16 Hz) as well as in the 0.25-3, 3-6 and 6-9 Hz frequency bands was observed. The behavioural and electrocortical effects of interleukin-2 were blocked in animals pretreated with anti-IL-2 monoclonal antibodies and with naloxone, whereas they were still evident in rats pretreated with yohimbine. In addition, the behavioural and electrocortical slow-wave sleep effects observed after the administration of interleukin-2 into the locus coeruleus were reduced significantly or antagonized completely by a previous pretreatment with pertussis toxin, forskolin, dibutyryl-cyclic-AMP and 8-bromo-cyclic-AMP. These results are consistent with the hypothesis that the behavioural and electrocortical changes of this lymphokine are mediated at locus coeruleus level via a guanine regulatory Gi protein coupling IL-2 specific receptors to the adenylate cyclase system.
 ...
PMID:Effects of pertussis toxin, dibutyryl-cyclic-AMP, bromo-cyclic-AMP and forskolin on the behavioural and electrocortical power spectrum changes induced by microinfusion of interleukin-2 into the locus coeruleus. 166 94

Human CD4+ T-cell clones specific for pertussis toxin and other Bordetella pertussis antigens have been tested for their cytotoxic activity, lymphokine production, and capacity to induce immunoglobulin synthesis. Clones specific for the S1 subunit of pertussis toxin were cytotoxic for autologous Epstein-Barr virus-transformed B cells, which had been pulsed with the native antigen, the recombinant S1 subunit of pertussis toxin, or synthetic peptides derived from the S1 amino acid sequence. The killing of antigen-pulsed target cells was class II restricted. All of the T-cell clones produced mostly interleukin-2 and gamma interferon and assisted allogeneic B cells in the production of immunoglobulins M and G but not immunoglobulin E. The potential in vivo role of the cytotoxic activity of these clones is discussed.
 ...
PMID:Lymphokine secretion and cytotoxic activity of human CD4+ T-cell clones against Bordetella pertussis. 171 14

The anti-human serum albumin (HSA) B-cell repertoire of C57BL/6 mice was examined by culturing splenocytes at limiting dilution following polyclonal stimulation with Escherichia coli lipopolysaccharide and a lymphokine mixture. The frequency of anti-HSA precursors was determined before and after immunization with alum-precipitated HSA and 10(9) killed Bordetella pertussis organisms, by submitting clonal supernatants to an ELISA. Anti-HSA IgG1-forming precursors were rare in unimmunized spleens, representing approximately equal to 1 in 500,000 splenocytes or only approximately equal to 100 cells per spleen. Between day 5 and day 7 after immunization, this figure increased to approximately equal to 20,000 cells per spleen. Over the following 3 weeks, there was a progressive increase in the mean optical density generated in the clonal ELISA, presumably due to affinity maturation of the B-cell population. When freshly deaggregated HSA was injected before or even up to 4 days after challenge immunization, the appearance of anti-HSA IgG1-forming cell precursors was largely prevented. The effect was most marked with 5 mg or 1 mg of soluble HSA, but impressive partial effects could be seen with as little as 10 micrograms of HSA if administered before challenge immunization. Most of the few clones seen after the higher doses of the toleragen appeared to make antibody of low affinity. The capacity to influence the B-cell pool by soluble antigen administered just 1-2 days before the sudden appearance of IgG1 precursors argues against the totality of the effect being due to T-cell-mediated suppression and in favor of a direct effect on B cells.
 ...
PMID:Soluble antigen abrogates the appearance of anti-protein IgG1-forming cell precursors during primary immunization. 230 21

T helper cells reactive to myelin basic protein are clearly implicated in the pathogenesis of murine EAE. We have developed a T cell line, BML-1 that (1) is reactive to the encephalitogenic amino terminal nonapeptide (1-9NAC) of MBP, (2) is I-Au restricted, and (3) induces relapsing EAE in B10.PL (H-2u) mice. Measurement of the lymphokine profile of BML-1 revealed secretion of IL-2, interferon-gamma and lymphotoxin but not IL-4. This profile is consistent with the Th1/DTH subtype. Coculture of BML-1 with MBP-primed B cells shows that BML-1 does not provide significant helper function in vitro. In addition, BML-1 secretion of interferon-gamma was found to inhibit LPS-induced anti-MBP antibody responses. This suggested that anti-MBP antibodies may not be necessary for induction of EAE. Sera from mice, in which severe disease was induced with the 1-9NAC peptide and Bordetella pertussis, showed no development of serum antibodies to MBP. These data show that MBP-reactive Th cells of the Th-1/DTH subtype can induce EAE and do not provide Th function for anti-MBP responses and that serum anti-MBP antibodies are not found in peptide 1-9NAC-induced disease. T cell lines specific for encephalitogenic epitopes and characterized for lymphokine secretion will provide a useful tool for understanding the role of T cells in the induction of EAE.
 ...
PMID:Encephalitogenic T cells in the B10.PL model of experimental allergic encephalomyelitis (EAE) are of the Th-1 lymphokine subtype. 247

The binding of interleukin 2 (IL 2) to specific cell surface receptors provides a unique proliferative stimulus to sensitive T-lymphocytes. The purpose of this investigation was to examine the hypothesis that IL 2 stimulus-response coupling in the IL 2-dependent murine T-lymphocyte clone CTLL-2 employed some of the intracellular second messengers used by other growth factors. No evidence was obtained to implicate changes in intracellular Ca2+ concentrations, protein kinase C activation, or stimulation of the Na+/H+ antiporter or the Na+/K+ ATPase as requirements for stimulation by recombinant human IL 2. Pertussis toxin did not inhibit IL 2-driven growth of CTLL-2, and while cholera toxin did inhibit growth, its effect was optimal 6 to 8 hr after addition of IL 2 and could be mimicked by increased intracellular cyclic-AMP. Thus, guanine nucleotide-binding regulatory proteins do not appear to be involved in stimulation by this lymphokine. Together, these data suggest that IL 2 may not use any of the same types of intracellular second messengers generated subsequent to the binding of antigen or mitogen by T-lymphocytes.
 ...
PMID:Does interleukin 2 stimulus-response coupling result in generation of intracellular second messengers? 284 44

Delayed tissue eosinophilia in DNP-ovalbumin-induced allergic inflammatory skin lesions of guinea pigs was markedly enhanced by previous treatment with alum hydroxy gel (Alum) or Bordetella pertussis vaccine. This enhancement seemed due to increased production of a lymphocyte-derived eosinophil chemotactic factor (ECF) at the skin site. Treatment of animals with Alum potentiated antigen-induced in vitro ECF production by lymphoid cells from spleen and mesenteric lymph node of sensitized animals. The co-culture supernatants of lymphoid cells from Alum-treated animals also potentiated concanavalin A (Con A)-induced in vitro ECF production. The potentiating effect of Alum on ECF production seemed to be ascribed to the release of soluble factors from macrophages of the Alum-treated animals. The macrophage-derived soluble factor ECF-potentiating factor (ECF-PF) selectively potentiated ECF production but not macrophage chemotactic lymphokine production by Con A-stimulated lymphoid cells from normal animals. ECF-PF activity was associated with two separate m.w. fractions: one was 50,000 to 70,000 and the other was 10,000 to 20,000. The present study provides one of the explanations for enhanced ECF production by adjuvants, such as Alum and Bordetella pertussis vaccine.
 ...
PMID:Selective regulation of chemotactic lymphokine production. I. Selective potentiation of eosinophil chemotactic lymphokine production in alum hydroxy gel- and Bordetella pertussis vaccine-treated guinea pigs. 286 77

The effects of lymphokine production of two agents known to potentiate delayed-type hypersensitivity (DTH), pertussigen (pertussis toxin) (PT) and cyclophosphamide (CY) have been investigated. These two agents were administered to immunized mice. Subsequently, lymph nodes and spleen cells were exposed to specific antigen in vitro. The resulting culture supernatants were assayed for the presence of lymphokines. Only supernatants of cells from the mice given PT contained appreciable quantities of interferon-gamma (IFN-gamma) and stimulated cells of the monocyte-like WEHI-265 cell line to produce procoagulant activator and plasminogen activator. On the other hand, CY was more effective than PT on the production of interleukin-3 (IL-3). Both adjuvants had small enhancing effects on the production of interleukin-2 (IL-2). With either adjuvant, the cell populations induced had a similarly enhanced capacity to transfer DTH. These results demonstrate that the capacity of cells to transfer DTH does not necessarily correlate with their release of particular lymphokines. The potentiation of DTH by cyclophosphamide did not depend on significantly enhanced generation of IFN-gamma, procoagulant activator, or plasminogen activator. The amount of IFN-gamma in the culture supernatants correlated with their capacity to produce procoagulant activator and plasminogen activator, whereas the amount of IL-2 and IL-3 did not.
 ...
PMID:Potentiation of delayed-type hypersensitivity by pertussigen or cyclophosphamide with release of different lymphokines. 312 25

Pertussigen is a protein toxin of Bordetella pertussis that acts as a powerful stimulator of the intensity and duration of delayed-type hypersensitivity (DTH) in mice. This study describes the potent in vivo effect of pertussigen on the levels of antigen-specific macrophage-activating lymphokine(s); lymphokine(s) was measured by the stimulation of macrophage procoagulant activity (mPCA), or plasminogen activator (PA) activity. Lymphoid cells were removed from immunized animals and cultured with specific antigen, keyhole limpet hemocyanin, ovalbumin, or human gamma-globulin. The culture supernatants were then incubated with the monocyte-like cell line WEHI-265 to measure mPCA or with WEHI-265 or resident peritoneal macrophages to measure PA activity. Mice were given pertussigen at the time of immunization, and the subsequent generation by lymphocyte supernatants of both of these macrophage activities proved to be greatly enhanced; the effect of pertussigen was antigen specific. Pertussigen thus induces an increase in lymphokine(s) production responsible for the in vitro increase in macrophage mPCA and PA activity and which may be responsible for some of the potent immune effects of this agent in vivo.
 ...
PMID:Pertussigen in vivo enhances antigen-specific production in vitro of lymphokine that stimulates macrophage procoagulant activity and plasminogen activator. 378 90

Effects of pertussis toxin (PT) on sensitized T-cell populations for delayed-type hypersensitivity (DTH) were examined in mice. DTH was induced by sensitizing mice with ovalbumin (OA) and elicited by injecting OA into the footpad. DTH could be conferred on naive recipient mice by injecting sensitized spleen cells either intravenously into mice or locally into the footpad. When the sensitized mice were given PT at the time of DTH-elicitation, they did not express a high DTH reaction, with the maximum reaction 24 hr after elicitation. When the recipient mice were given PT just before intravenous injection of sensitized spleen cells, DTH was not conferred. In addition, when the sensitized spleen cells were treated with PT in vitro and then transferred intravenously, DTH was not conferred in recipient mice. However, DTH was conferred by local transfer of the sensitized spleen cells even after treatment with PT in vitro. Migration experiments using 51Cr-labeled, sensitized splenic T cells demonstrated that PT treatment of the T-cell population inhibited its accumulation in the DTH reaction site 24 hr after intravenous transfer. On the other hand, experiments on in vitro lymphokine production by the sensitized splenic T cells demonstrated that the PT treatment did not inhibit antigen-dependent production of a macrophage activating factor (MAF). These results suggest that PT suppresses the migration of the sensitized T-cell population from the circulation of the DTH reaction site but not their MAF production. Based on these findings, possible mechanisms by which PT affects DTH are discussed.
 ...
PMID:Effects of pertussis toxin (PT) on T-cell populations sensitized for delayed-type hypersensitivity in mice. 660

Previously, the authors have described a molecule, identified by the LD6 monoclonal antibody (MoAb), present at the cell surface of long-term cultured T and Natural Killer (NK) cells which is involved in cell triggering. In the study described here the authors used biotin surface labelling and immunoprecipitation to show that LD6 MoAb recognizes a surface protein of approximately 65 kDa. In combination with submitogenic concentrations of phorbol esters (PMA); LD6 MoAb was able to induce accumulation of mRNA specific for GM-CSF, gamma-IFN and TNF-alpha and release of these cytokines by LD6+ T-cell lines. Both lymphokine production and lymphokine-specific mRNA accumulation induced by the LD6 MoAb were blocked totally by Cyclosporin A (CsA). To investigate the mechanism(s) of signal transduction through this activatory pathway, the authors performed Ca++ mobilization experiments. The results of these experiments suggested a role for Ca++ in signal transduction. The Ca++ mobilization induced by LD6 MoAb cross-linking could be inhibited totally by the use of pertussis toxin, indicating a possible role for G proteins in signalling through the LD6 MoAb-reactive molecule. Western blot analysis performed with an anti-phosphotyrosine antibody did not suggest that tyrosine kinase activation has a role.
 ...
PMID:Characterization of a cyclosporin A-sensitive activation pathway in cultured T and natural killer cells. 814 96


1