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)

The mitogenic response of murine lymphocytes to the lymphocytosis-promoting factor of Bordetella pertussis has been shown to be due to activation of T cells. The selectivity of responsiveness to LPF with respect to the population of T cells which is stimllated, differs from that of PHA as well as Con A, and the surface receptors are different. A population of adherent cells, which does not appear to consist of macrophages or other phagocytic cells, is required for the T-cell response.
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PMID:The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes: II. Nature of the responding cells. 18 16

Mice exposed to a sublethal dose of X-rays were immunized with alum-precipitated DNP-KLH (dinitrophenyl-keyhole limpet haemocyanin) and B. pertussis either before or after irradiation. The primary anti-DNP antibody response was evaluated during 8 weeks after immunization by the equilibrium dialysis technique using ammonium sulphate- precipitated serum globulins and the ligand 3H-labelled xi-DNP-L-Lysine. The serum concentrations of antibody sites in mice immunized 1-5 days before or 2 h-8 weeks after 450 rad were below the values in unirradiated controls at all bleeding times. Antibody affinity, however, was found to be up to 20 fold higher in irradiated mice than in control mice when antigen was injected before, or 3-8 weeks after, irradiation. Spleen cells from mice exposed to 450 rad 1-9 weeks before killing were stimulated in vitro with PHA, ConA, or LPS. Recovery profiles of mitotic responsiveness suggest that enhancement of antibody affinity in irradiated mice could result from relative lack of suppressor T Cells.
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PMID:Effects of whole-body irradiation on antibody affinity. 19 58

An immunological study in a case of nephrotic syndrome in early infancy with mesangioproliferative glomerulonephritis with focal crescents revealed deficiencies in humoral and cellular immunity. Serum Ig-G antibody levels such as pertussis-agglutinins, tetanus and diophtheria-antitoxing were decreased. A loss of tetanus antibodies in the urine could be observed. The production of tetanus-antibodies after immunogenic stimulation with tetanus-antigen was not diminished. The loss of Ig-A in the urine might have been compensated by a higher synthesis rate, which could also be the cause of the increased serum levels of Ig-M, since a loss of Ig-M in urine was not observed. The diminished serum levels of Ig-G antibodies were considered not only to be the result of loss, but possibly also of higher catabolism, and an insufficient compensation by a higher rate of synthesis. The percentage of T-cells in peripheral blood was found to be low. Stimulation of lymphocytes with PHA was at first normal, but in the last investigations diminished. Special experiments lead to the assumption, that this partial defect of cellular immunity might be the result of lacking or diminution of nutritive plasmafactors.
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PMID:[Immunological studies in a case of congenital nephrotic syndrome with focal extracapillary proliferative glomerulonephritis (author's transl)]. 30 66

Neoplastic Jurkat cells were submitted to a PHA stimulation test after a preincubation in maternal or nulliparous serum (10% dilution). The Il2R expression was significantly downregulated among maternal serum treated cells. Retroplacental serum was significantly more inhibitive than peripheral maternal serum (P less than 0.01). The maternal IgG fractions and mostly the retroplacental IgG fraction proved to contain a factor mainly responsible for the Il2R expression inhibitive property. The molecular mechanism of this phenomenon was further studied. It was shown that H7 (acting as a protein kinase inhibitor) could not influence the Il2R modulation. E.G.T.A., a calcium chelator, was not able to interfere with the inhibitive influence of maternal serum. It was suggested that the maternal serum mediated inhibition of the IL2R expression is not influenced by the hydrolysis of membrane bound phosphatidyl inositol. In contrast, pertussis toxin markedly enhanced, in a dose dependent way, the suppressive influence of maternal serum as compared to nulliparous serum. At low concentrations, pertussis toxin lost its stimulating property and retained its ability to ADP ribosylate the alpha subunit of G proteins inducing a release of adenylcyclase mediating cAMP synthesis. This mechanism has been further studied by the addition of dbc AMP or dbc GMP to Jurkat cells preparations stimulated by PHA. dbc AMP, in a dose-related way, induced a downregulation of the IL2R expression of stimulated neoplastic cells preincubated in nulliparous or maternal serum. dbc GMP did not influence the IL2R expression in the same experimental conditions. The maternal serum mediated cells showed the most pronounced IL2R inhibition. Finally, it was shown that the cAMP synthesis by PHA stimulated Jurkat cells was upregulated in a dose dependent way, after a previous cellular incubation in progressive concentrations of maternal serum. In contrast, among nulliparous serum pretreated cells, cAMP synthesis remained significantly lower, after a lectin stimulation, as compared to the cAMP production derived from retroplacental serum treated and stimulated cells. Taken together, these experiments suggest that the maternal serum dependent suppression of the IL2R expression is related to a protein G stimulation followed by an enhanced cAMP synthesis.
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PMID:Mechanism of action of maternal serum on the interleukin2 receptor expression. 132 91

The histamine release induced by compound 48/80, bradykinin or polyethylenimine with a molecular weight of 600 (PEI6) was inhibited by wheat germ agglutinin (WGA) and phytohemagglutinin E-subunits (PHA-E4), and the inhibition was specifically reversed by N-acetyl glucosamine and N-acetyl galactosamine, respectively. Concanavalin A (Con A) and phytohemagglutinin L-subunits (PHA-L4) did not inhibit the histamine release induced by compound 48/80, bradykinin or PEI6. The histamine release induced by substance P was also inhibited sugar-specifically by WGA and PHA-E4. The binding sites for compound 48/80, bradykinin, PEI6 and substance P, therefore, seemed to especially overlap each other. These binding sites were found to be glycoproteins having affinities to WGA and PHA-E4, but not to Con A and PHA-L4. The binding of WGA and PHA-E4 to the glycoproteins resulted in inhibition of the interaction between the basic secretagogues including bradykinin and substance P and their binding sites on the mast cells. The bindings of five lectins to mast cell glycoproteins were examined by lectin-blotting. Several glycoproteins, which had specific affinities to WGA and PHA-E4, but not to Con A and PHA-L4 were detected. We assumed that the binding sites for basic secretagogues which are coupled with histamine-releasing mechanisms exist among these glycoproteins. A 41-kDa protein (alpha-subunit of pertussis toxin-sensitive G protein) was not detected by WGA, suggesting that the binding sites for the basic secretagogues were not G proteins.
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PMID:Sugar-specific inhibitory effects of wheat germ agglutinin and phytohemagglutinin-E4 on histamine release induced by basic secretagogues from rat peritoneal mast cells and their possible action sites. 172 87

Multiple effects of pertussis toxin (PT) on Jurkat T-cells can be distinguished on the basis of their dose-response and their kinetics. High concentrations of PT deliver to cells an activating signal resulting in a rapid rise in [Ca2+]i followed by IL-2 synthesis. This activation is accompanied (within 2 h) by a down-regulation of the CD3/TCR complex from the cell surface. Cells then become refractory towards stimulation by CD3 mAb or PHA. All these effects, referred to as 'mitogenic effects', present the same dose-response curves with an EC50 of 0.5 micrograms/ml. Short term effects (PT-induced Ca2+ movements, down-regulation of CD3/TCR complex and inhibition of PHA and CD3-induced Ca2+ signal) are observed under conditions where no PT-induced ADP-ribosylation can be detected. In contrast, ADP-ribosylation of the 40,000 alpha-subunit of G-proteins requires a sustained (18 h) incubation of intact cells in the presence of low concentration (EC50 = 0.3 ng/ml) of PT. Dose-response curves for PT-dependent ADP-ribosylation and mitogenic effects are separated by three orders of magnitude. Covalent modification of G-protein has no effect on CD3-induced increase in [Ca2+]i and IL-2 synthesis induced by a combination of phorbol ester and either CD3 mAb, PHA or calcium ionophore. These data indicate that transduction of the mitogenic signal does not involve a PT-sensitive G-protein. Furthermore, inhibition of mitogenic signals following PT treatment results from a PT-induced activation leading to a down-regulation of the CD3/T cell receptor complex.
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PMID:Pertussis toxin-sensitive G-proteins are not involved in activation of T-lymphocytes. 182 86

Pertussis toxin (PT) has previously been shown to affect a wide variety of immune responses and to cause lymphocyte proliferation. We have investigated the biochemical basis for the mitogenic activity of PT by using human peripheral blood lymphocytes. PT was found to induce a rapid rise in cytosolic free calcium concentration and an alkalinization of the cytosol through the Na+/H+ antiporter. The toxin was also found to induce expression of IL-2-receptor on CD3+ cells and to stimulate IL-2 production. PT induced proliferation of both CD4+ and CD8+ T cells in the presence (but not in the absence) of accessory cells. PT also stimulated IL-1 production by monocytes but neither IL-1, IL-6 alone nor a combination of the two lymphokines could replace accessory cells suggesting that cell:cell contact is required. Low doses of PT induced ADP-ribosylation of G proteins but this treatment did not affect significantly PHA-induced [Ca2+]i increase and IL-2-induced DNA synthesis suggesting that the substrates of the ADP-ribosyltransferase activity of PT are not involved in the signalling pathways leading to DNA replication.
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PMID:Pertussis toxin-induced mitogenesis in human T lymphocytes. 190 37

The importance of increases in [Ca2+]i, stimulation of Na+/H+ exchange, and turnover of membrane phospholipids as signals for mitogen-induced activation of human T cells has been reviewed. In the presence of optimal concentrations of lectin and appropriately presented antigen, T cells increase [Ca2+]i, secrete IL2, express IL2 receptors and later divide. An increase in [Ca2+]i is critical for IL2 secretion in contrast to the requirements for IL2 receptor expression and IL2-IL2 receptor interaction. Treatment of T cells with TPA appears to bypass the requirement for an increase in [Ca2+]i for IL2 secretion and cell proliferation, indicating that various mitogens can trigger T cells through both [Ca2+]i-dependent and [Ca2+]i-independent pathways. Influx of Ca2+ from the extracellular milieu appears essential for the induced increase in [Ca2+]i associated with IL2 secretion. These increases in [Ca2+]i, which are correlated with the degree of lymphoproliferation and IL2 secretion, are sensitive to changes in membrane potential. The changes in [Ca2+]i are not mediated by the opening of voltage-gated K+ channels but the nature of the potential-sensitive event remains to be determined. The membrane potential effects may be mediated through the gating of a putative Ca2+ channel or by affecting the inward electrochemical Ca2+ gradient. It is clear that lymphoid cells of both T and B lineage possess a functional Na+/H+ antiport, which plays a central role in the regulation of pHi. It is also generally agreed that the antiport can be stimulated by mitogens, co-mitogens and by agents that induce differentiation. The meaning of this stimulation is not, however, entirely understood. It may be an essential signal or link in the series of events triggered by the binding of ligands to their membrane receptors. Alternatively, it may represent an ancillary event, intended to increase H+ ejection in anticipation of an increased metabolic rate. Finally, a third possible reason for the stimulation of Na+/H+ exchange could be to increase the osmotic content of the cells, inducing cell swelling that may be an early requirement for cellular growth. Indeed, amiloride-sensitive cellular swelling has been detected electronically following treatment of T lymphocytes with TPA (Grinstein et al. 1985a). PHA is a potent activator of phosphatidylinositol hydrolysis. In other cell types, receptors are coupled to phospholipase C by a G protein(s). However, the transducing mechanism in human peripheral blood lymphocytes does not appear to be a pertussis toxin-sensitive G protein(s).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Transmembrane ion fluxes during activation of human T lymphocytes: role of Ca2+, Na+/H+ exchange and phospholipid turnover. 243 15

Stimulation of the T-cell line JURKAT with PHA or anti-T3 antibody leads to a rapid and sustained rise of cytosolic free Ca2+, as determined by quin2 fluorescence measurements. Pertussis toxin and N-ethylmaleimide, substances known to inactivate a regulatory N-protein, caused partial to complete inhibition of the cytosolic free Ca2+ response induced both by anti-T3 or PHA. The high cytosolic free Ca2+ level induced by anti-T3 or PHA declined more rapidly after addition of phorbol ester, phorbol myristate acetate (PMA). PMA did not affect cytosolic free Ca2+ changes induced by ionomycin indicating that the effect of PMA is due to a direct inhibitory effect on a transduction mechanism and not to activation of Ca2+ extrusion. Our data suggest that a regulatory N-protein is involved in the transduction of the PHA and anti-T3 response into a rapid and sustained elevation of cytosolic free Ca2+. Activation of protein kinase C by PMA modulates the calcium response in JURKAT cells, suggesting that protein kinase C may be involved in feedback regulation of the transduction mechanism.
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PMID:Characterization of PHA and anti-T3 induced transduction mechanisms in a human T-cell leukaemia line. 349 99

Formation of lymph follicles in draining popliteal lymph nodes was examined in 8-week-old, male C57Bl/6 mice which had been injected in the rear footpad with any one of eleven test substances including thymus-dependent and thymus-independent antigens, and killed after 6-14 days. HGG (10-100 micrograms), MGG, tetanus and diphtheria toxoids (2-10 Lf) and influenza HA vaccine (35 CCA) induced germinal centers in association with existing follicles, but failed to produce new follicles in draining nodes. KLH (10-100 micrograms), SRBC (1 X 10(8)) and formalin-killed pertussis organisms (5 X 10(8)) induced germinal centers in existing follicles and also produced new follicles which soon developed germinal centers. Levan and PVP (10-100 micrograms) induced neither germinal centers nor new follicles. Ferritin (100 micrograms) virtually failed to induce germinal centers but produced a significant number of new primary follicles. In further experiments, artificially aggregated substances were examined with regards to their ability of inducing lymph follicle formation in draining nodes. Precipitated proteins such as alum-precipitated PHA, HGG, tetanus and diphtheria toxoids, "Sepharose"-PHA and "Sepharose"-HGG induced a significant number of new follicles. These observations suggest that efficient follicle formation is associated with particulate and high-molecular-weight antigens which are liable to be phagocytized, whereas soluble, poorly phagocytized antigens tend to be inefficient. Soluble proteins may be effective if given in precipitated form. Thymic dependency appears to be irrelevant. The present results point to a possible participation of macrophages in the mechanism of follicle formation.
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PMID:Formation of lymph follicles in draining lymph nodes after local injection of various antigenic substances in mice. 352 2


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