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)

Apoptosis of natural killer (NK) cells can be induced by non-specific physical damage (UV irradiation, heat shock) or by simultaneous ligation of the CD16 and the interleukin-2 receptor (IL-2R) molecules, but not with either anti-CD16 or IL-2 alone. Whereas blockade of GTP-binding protein (G protein)-mediated signal transduction using ADP-ribosylating bacterial toxins or the GTPase-resistant GTP analog guanosine 5'-0-(3-thiotriphosphate (GTP gamma S) does not affect non-specific induction of NK cell apoptosis, such interventions do inhibit induction of apoptosis by anti-CD16/IL-2. The G proteins involved in the regulation of activation-induced NK apoptosis are sensitive to pertussis toxin (PTX) and to the non-specific GTP analog GTP gamma S but not to cholera toxin, Pseudomonas exotoxin A or diphtheria toxin. A pertussis toxin mutant that lacks ADP-ribosylating activity, but conserves the membrane translocating and T cell-mitogenic effects of the native molecule, fails to inhibit NK apoptosis. To exert their apoptosis-inhibitory effect, PTX and GTP gamma S must be employed before cells are activated. Later addition has no effect, suggesting the implication of G proteins in the transmission of apoptosis-inducing signals, but not in the effector stage of apoptosis. Pre-incubation with PTX or GTP gamma S does not affect the activation of NK cells by CD16 cross-linking, IL-2 stimulation- or both, as assessed by the induction of CD69 expression, protein tyrosine phosphorylation and calcium mobilization. Moreover, neither PTX nor GTP gamma S compromise the effector function of NK cells or the susceptibility of target cells to NK-mediated lysis. These data suggest apoptosis as a novel mechanism by which NK responses may be controlled in vivo, as well as an experimental and therapeutical strategy to counteract endogenous down-regulation of NK responses.
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PMID:Pertussis toxin-sensitive GTP-binding proteins regulate activation-induced apoptotic cell death of human natural killer cells. 748 48

The C-C chemokines MIP-1 alpha, MCP-1, and RANTES, but not MIP-1 beta, induce the chemotaxis of NK and IL-2-activated NK (IANK) cells, as determined in microchemotaxis assay. Only RANTES and MCP-1, but not MIP-1 alpha were able to induce the chemokinesis of NK cells. In contrast, none of the C-C chemokines tested was able to induce the chemokinesis of IANK cells. IANK cell chemotaxis in response to MCP-1 or RANTES but not MIP-1 alpha, was inhibited by pertussis toxin (PT). In contrast, cholera toxin (CT) inhibited the ability of all three chemokines to induce the chemotaxis of IANK cells. IANK cells intoxicated with PT lost their ability to migrate in response to RANTES and MCP-1 but not MIP-1 alpha, whereas those intoxicated with CT lost their ability to migrate in response to the three C-C chemokines tested. These results suggest that guanine nucleotide binding (G) proteins are coupled to C-C chemokine receptors in IANK cells. Subsequently, we observed that MIP-1 alpha, MCP-1, and RANTES, but not MIP-1 beta, enhance the binding of guanosine 5'-O-(thiotriphosphate), and increase the hydrolysis of [32P]GTP in IANK cell membranes. Further analysis showed that MIP-1 alpha, RANTES, or MCP-1 did not enhance GTP binding in membranes prepared from IANK cells intoxicated with CT, whereas only RANTES and MCP-1 but not MIP-1 alpha lost their ability to enhance GTP binding to IANK cell membranes prepared from PT-intoxicated cells. The differential inhibitory activity of CT and PT suggests that C-C chemokine receptors are coupled to different G proteins in IANK cells.
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PMID:C-C chemokines induce the chemotaxis of NK and IL-2-activated NK cells. Role for G proteins. 752 19

We reassessed the involvement of Bordetella pertussis toxin (PTX)-sensitive proteins in the IL-1 signaling pathway on the responses induced by IL-1 on the murine thymoma cell line EL4 6.1. We demonstrate that the ADP-ribosyltransferase activity of PTX, and not its cell-anchoring B oligomer part, is responsible for the inhibition of IL-1-induced IL-2 release, since 1) the concentration of PTX (< or = 1 ng/ml) required to block the secretion is 100 to 1000 times lower than the concentration needed with the B oligomer; and 2) the mutated PT-9K/129G, devoid of ADP-ribosyltransferase activity, was inactive at 100 ng/ml. We found that partial ADP-ribosylation of the Gi2/Gi3 proteins before stimulation with IL-1 was sufficient to obtain full inhibition of IL-2 release. PTX did not however inhibit the appearance on the cell surface of the high affinity IL-2 receptors or the IL-2 release induced by PMA. In addition, we show that PTX prevented the expression of the IL-2 mRNA induced by IL-1, without affecting the binding of IL-2 specific nuclear factors to the T cell distal element of the IL-2 promoter. Furthermore, PTX also inhibited IL-1-induced proliferation of non-transformed thymocytes. In conclusion, our results demonstrate that IL-1-induced IL-2 release is sensitive to PTX-catalyzed ADP-ribosylation and that IL-1 activates a diverging pathway on EL4 6.1 cells.
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PMID:IL-1 stimulates a diverging signaling pathway in EL4 6.1 thymoma cells. IL-2 release, but not IL-2 receptor expression, is sensitive to pertussis toxin. 760 94

The intranasal (i.n.) immunization of mice with Bordetella pertussis filamentous haemagglutinin (FHA) either as a solution or incorporated in biodegradable microparticles induced very similar immune responses. Both resulted in strong systemic IgG responses to FHA and good levels of anti-FHA IgG and IgA in the lungs of immunized mice. In comparison, the intraperitoneal (i.p.) immunization of mice with FHA, as a solution, engendered anti-FHA antibody responses which were stronger for serum IgG, similar for lung IgG and lower for lung IgA. The anti-FHA antibody levels, as measured by immunosorbent assay, were shown to correlate with their functional activity in the blocking of B. pertussis adhesion to HeLa tissue-culture cells. All three forms of immunization appeared to stimulate T-cell responses as assessed by in vitro antigen-specific spleen cell proliferation and IL-2 secretion indicative of a Th1 type response, however, cells from i.p. immunized mice only secreted low levels of IL-5. All three methods of FHA immunization provided mice with significant protection against subsequent aerosol challenge with virulent B. pertussis. Mice which had been immunized intra-nasally eliminated the bacteria from their lungs slightly more rapidly than i.p. immunized mice, demonstrating the efficacy of intranasal administration of FHA in solution and in the more practical biodegradable microparticle form.
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PMID:Immune responses and protection against Bordetella pertussis infection after intranasal immunization of mice with filamentous haemagglutinin in solution or incorporated in biodegradable microparticles. 763 14

Tyrosine phosphorylation of the cellular proteins of IL-2-stimulated NK cells was determined by anti-phosphotyrosine immunoblotting. IL-2 induced tyrosine phosphorylation of a 105-110 kDa protein in a dose-dependent manner. The tyrosine phosphorylation took place within 5 min after the addition of IL-2 to NK cells, and reached a maximal level in 15 min. The degree of the tyrosine phosphorylation correlated with IL-2-induced LAK activity. Staurosporine and pertussis toxin, which slightly suppressed LAK induction, did not inhibit tyrosine phosphorylation of the 105-110 kDa protein. Genistein, TMB-8 and EGTA completely inhibited LAK induction; however, the calcium channel blocker and chelator did not prevent the protein tyrosine phosphorylation. Anti-IL-2R beta mAb almost completely suppressed tyrosine phosphorylation of the 105-110 kDa protein, but anti-IL-2R alpha mAb only slightly suppressed it; this result correlated with that of the suppression of LAK activity. No further suppression of the tyrosine phosphorylation was induced even when both mAbs were added. Western blotting of the immunoprecipitates revealed no association of PLC-gamma 1 or IL-2R beta with the 105-110 kDa protein. These results suggest that both tyrosine phosphorylation of the 105-110 kDa protein and translocation of [Ca++]i are essential for NK-LAK induction, and the tyrosine phosphorylation plays a critical role in the early stage of IL-2 signalling from the IL-2R beta chain.
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PMID:NK-LAK induction with IL-2 is regulated by tyrosine phosphorylation of a 105-110 kDa protein. 775 Sep 84

Under certain physiological and pathological conditions, natural killer (NK) cells rapidly accumulate in tissues. Chemokines are an essential component of the current paradigm of leukocyte recruitment. The present study was designed to investigate the responsiveness of NK cells to the prototypic C-C chemokine, monocyte chemotactic protein-1 (MCP-1). MCP-1 induced migration across filters of interleukin (IL)-2-activated NK cells, whereas it was a weak attractant for unstimulated cells. Maximal induction of migration required a positive concentration gradient between the lower and the upper compartment of the chemotaxis chamber. Preliminary characterization of the MCP-1 receptor on NK cells indicated that the chemotactic response to MCP-1 was blocked by pre-treatment of cells with Bordetella pertussis toxin, and MCP-1 but not IL-8 displaced 125I-labeled MCP-1 from IL-2-activated NK cells. The related chemokines MCP-2 and MCP-3 were also active--though less potent--attractants for activated NK cells. Thus the spectrum of action of MCP-1, -2 and -3 encompasses NK cells and chemokines are likely to play a role in regulating extravasation of these cells.
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PMID:Induction of natural killer cell migration by monocyte chemotactic protein-1, -2 and -3. 780 52

In lymphocyte cultures, IgE production was achieved by stimulating T cells with anti-CD2 and IL-2. Here we show that anti-CD28, in the presence or absence of IL-2, reduces this IgE production approximately 10-fold. This inhibition of IgE production was almost completely reversed by Pertussis toxin (PT). PT had no effect on IgE production when the cells were stimulated in the absence of anti-CD28. No major effects of PT were found on IgM production. PT had no effect on purified B cells, stimulated with IL-4 and anti-CD40. In the presence of saturating amounts of rIL-4 similar results were obtained, albeit the absolute amounts of IgE produced were higher in all situations. Furthermore, PT-induced IgE production was still dependent on IL-4, as was evident from experiments in which anti-IL-4 was added to the culture. The IgE enhancing effect was dependent on the adenosine diphosphate (ADP)-ribosyltransferase activity of PT, because a mutant molecule lacking this activity was not able to restore anti-CD28-induced inhibition of IgE synthesis. Thus, we show that co-stimulation with anti-CD28 causes an inhibition of T cell-dependent IgE production by B cells, which inhibition can be specifically overcome by PT. An analysis of the molecular pathways underlying this phenomenon may contribute to our understanding of the regulation of IgE synthesis in (patho)physiological conditions.
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PMID:Co-stimulation of T cells via CD28 inhibits human IgE production; reversal by pertussis toxin. 788 71

The effect of IL-8 on the in vitro locomotion of human IL-2-activated natural killer (IANK) cells was studied. It was observed that IL-8 induces chemokinesis in these cells, as determined by their migration in modified Boyden chambers. Bacterial toxins such as cholera toxin or pertussis toxin inhibited IL-8-induced chemokinetic activity, suggesting the involvement of guanine nucleotide-binding (G) proteins in IL-8 signal transduction in these cells. Pertussis toxin ADP-ribosylates a 39-kDa protein, whereas cholera toxin ADP-ribosylates a 43- to 45-kDa protein. Pretreatment of IANK cell membranes with 0.01 or 0.1 ng/ml of IL-8 and/or 5 microM GTP-gamma S did not affect pertussis toxin- or cholera toxin-dependent ADP-ribosylation. Western blot analysis showed that IANK cell membranes possess one Gi (39 kDa), two Gs (43 kDa and 45 kDa), and one Go (39 kDa). Pretreatment of IANK cell membranes with concentrations between 0.001 to 1.0 ng/ml of IL-8 resulted in the disappearance of the 39 kDa Go, but not Gi or Gs protein(s), suggesting that IL-8 receptors expressed on IANK cells are coupled to Go. Various concentrations of IL-8 enhanced the binding of GTP-gamma 35 S to IANK cell membranes, which further indicates the coupling of G proteins to IL-8 receptors in IANK cells.
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PMID:IL-8 induces the locomotion of human IL-2-activated natural killer cells. Involvement of a guanine nucleotide binding (Go) protein. 838 37

Transforming growth factor (TGF)-beta 1 induced rat IL-2-activated natural killer (IANK) cell chemotaxis. Various doses of cholera toxin (CT) or pertussis toxin (PT) inhibited the activity of TGF-beta 1 suggesting a role for guanine nucleotide binding (G) proteins. ADP-ribosylation assay showed that rat IANK cell membranes possess a 39 kDa PT substrate and two, 41 and 42 kDa, CT substrates. ADP-ribosylation also showed that incubating IANK cell membranes with TGF-beta 1 in the presence of guanosine 5'-O-(3-thiotriphosphate) resulted in the disappearance of the PT substrate. Immunoblot analysis showed that rat IANK cell membranes possess one Gi (39 kDa), one G0 (39 kDa) and three Gs (40, 41, and 42 kDa) proteins. Pretreatment of IANK cell membranes with TGF-beta 1 in the presence of guanosine-5'-O-(3-thiotriphosphate) reduced the intensity of the 39 kDa G(0) and the 40 kDa Gs but not the 39 kDa Gi or the 41 kDa or 42 kDa Gs. Furthermore, TGF-beta 1 stimulated GTP binding and increased GTPase activity in IANK cell membranes. Both activities were inhibited by PT or CT. This inhibition was associated with the modification of G proteins by the toxins suggesting that bacterial toxin substrates are linked to TGF-beta 1 receptors. Our results suggest that G0 and Gs are involved in mediating the chemotactic signal of TGF-beta 1 in rat IANK cells.
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PMID:Guanine nucleotide binding proteins mediate the chemotactic signal of transforming growth factor-beta 1 in rat IL-2 activated natural killer cells. 839 79

To elucidate the role of specific proinflammatory cytokines in regulating airway responsiveness, we examined the effects and mechanisms of action of IL-1beta, TNF-alpha, and IL-2 on the beta-adrenoceptor- and postreceptor-coupled transmembrane signaling mechanisms regulating relaxation in isolated rabbit tracheal smooth muscle (TSM) segments. During half-maximal isometric contraction of the tissues with acetylcholine, relaxation responses to isoproterenol, PGE2, and forskolin were separately compared in control (untreated) TSM and tissues incubated for 18 h with IL-1beta (10 ng/ml), TNF-(alpha (100 ng/ml), or IL-2 (200 ng/ml). Relative to controls, IL-1beta- and TNF-alpha-treated TSM, but not IL-2-treated tissues, depicted significant attenuation of their maximal relaxation and sensitivity (i.e., -log dose producing 50% maximal relaxation) to isoproterenol (P < 0.001) and PGE2 (P < 0.05); whereas the relaxation responses to direct stimulation of adenylate cyclase with forskolin were similar in the control and cytokine-treated tissues. Further, the attenuated relaxation to isoproterenol and PGE2 was ablated in the IL-1beta-treated TSM that were pretreated with either the muscarinic M2-receptor antagonist, methoctramine (10(-6) M), or pertussis toxin (100 ng/ml). Moreover, Western immunoblot analysis demonstrated that: (a) Gi protein expression was significantly enhanced in membrane fractions isolated from IL-1beta-treated TSM; and (b) the latter was largely attributed to induced enhanced expression of the Gi alpha2 and Gi alpha3 subunits. Collectively, these observations provide new evidence demonstrating that IL-lbeta and TNF-alpha induce impaired receptor-coupled airway relaxation in naive TSM, and that the latter effect is associated with increased muscarinic M2-receptor/Gi protein-coupled expression and function.
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PMID:Mechanism of cytokine-induced modulation of beta-adrenoceptor responsiveness in airway smooth muscle. 864 53


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