Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pretreatment of rat peritoneal mast cells, human basophils, bone marrow-derived mouse mast cells (BMMC) and mouse mast cell line PT-18 cells with 1 microgram/ml pertussis toxin (PT) failed to inhibit immunoglobulin E (IgE)-dependent histamine release from the cells. In BMMC and PT-18 cells, even 20-hr incubation of the cells with 1 microgram/ml PT, which ADP-ribosylates more than 97% of 41 kDa, alpha-subunit of Ni in the cells, failed to affect the IgE-dependent release of histamine or arachidonate. The results indicate that GTP-binding protein, Ni, is not involved in the transduction of triggering signals induced by cross-linking of IgE receptors. In contrast, pretreatment of rat mast cells with 1 ng/ml to 0.1 microgram/ml PT for 2 hr inhibited histamine release induced by compound 48/80 in a dose-dependent manner. A similar pretreatment with PT inhibited thrombin-induced histamine release from BMMC and N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced histamine release from human basophils in a similar dose-dependent fashion. However, even 20 hr of incubation of sensitized BMMC with 1 microgram/ml PT failed to inhibit either thrombin-induced or antigen-induced breakdown of phosphatidylinositides (PI), i.e., the formation of inositol triphosphate and diacylglycerol, Quin-2 signal, and the release of arachidonic acid. The results indicate that the inhibition of thrombin-induced histamine release by PT-treatment is not due to the inhibition of PI-turnover, and that Ni is not involved in thrombin-induced or antigen-induced (IgE-dependent) hydrolysis of phosphatidylinositides in mast cells.
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PMID:Effects of ADP-ribosylation of GTP-binding protein by pertussis toxin on immunoglobulin E-dependent and -independent histamine release from mast cells and basophils. 243 30

Incubation of rat peritoneal mast cells with substance P resulted in the transient stimulation of phosphoinositol breakdown and histamine secretion through an exocytotic process. These effects were inhibited markedly by a prior 2-hr exposure of the cells to pertussis toxin. Pertussis toxin also inhibited exocytosis induced by substance P, mastoparan and compound 48/80, but did not modify the secretory effect of the ionophore A23187. The transfer of rat peritoneal mast cells from balanced salt solution to calcium-free buffer led to a similar time-dependent decrease in their response to substance P and mastoparan. The concomitant absence of potassium from the calcium-free buffer enabled the mast cells to retain their secretory response. These data demonstrate identical dependency for calcium and monovalent ions of the secretory process elicited by substance P, mastoparan and compound 48/80. Pretreatment of mast cells with neuraminidase decreased the secretagogic effect of substance P, mastoparan and compound 48/80 without modifying the efficiency of the ionophore A23187. Thus, sialic acid residues might be involved in the initial binding of peptides and compound 48/80 to mast cells, which activate a pertussis toxin-sensitive G-protein and allows the increase in phospholipase C activity to induce exocytosis. This sequence of events might characterize the physiological pathway of mast cell activation by peptides, without necessarily requiring selective membrane receptors.
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PMID:Activation of rat peritoneal mast cells by substance P and mastoparan. 247 89

Incubation of rat mast cells with compound 48/80 resulted in transient breakdown of phosphatidylinositol 4,5-bisphosphate, rapid generation of inositol polyphosphates, 45Ca inflow, and the arachidonic acid liberation mainly from phosphatidylcholine, eventually leading to histamine secretion. All of these processes of signaling from Ca-mobilizing receptors to degranulation were markedly inhibited by prior 2-h exposure of cells to islet-activating protein (IAP), pertussis toxin. A23187 caused 45Ca inflow and releases of arachidonic acid and histamine without inducing breakdown of inositol phospholipids. The effects of A23187, in contrast to those of compound 48/80, were not altered by the exposure of cells to IAP. Incubation of the supernatant fraction of mast cell homogenates with the active component of IAP caused the transfer of the ADP-ribosyl moiety of added [alpha-32P]NAD to a protein with Mr = 41,000. The IAP-catalyzed ADP-ribosylation of this protein was prevented by guanosine 5'-(3-O-thio)triphosphate, indicating that this IAP substrate resembles, in character, the alpha-subunit of the guanine nucleotide regulatory protein (Ni) involved in inhibition of adenylate cyclase. The degree of ADP-ribosylation of this IAP substrate was prevented progressively by pre-exposure of the homogenate-donor cells to increasing concentrations of IAP. The half-maximally effective concentrations of the toxin were 0.2 to 0.6 ng/ml for all the IAP-sensitive processes studied. Thus, the ADP-ribosylation of the Mr = 41,000 protein occurring during exposure of cells to IAP appears to be responsible for the inhibition of signaling observed. It is proposed that the alpha-subunit of Ni, or a like protein, mediates signal transduction arising from Ca-mobilizing receptors, probably prior to Ca2+ gating.
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PMID:Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin. A possible involvement of the toxin-specific substrate in the Ca2+-mobilizing receptor-mediated biosignaling system. 257 78

The stimulatory effects of lymphokines, interleukin 3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 4 (IL-4), and the inhibitory effects of transforming growth factor beta (TGF-beta) and the pertussis toxin, islet activating protein (LAP), on multi-factor-dependent myeloid cell lines were examined. The effects of IL-3 on a mast cell progenitor clone, IC2 were indistinguishable from those of GM-CSF with respect to their concentration-response curves for induction of DNA synthesis and capability to maintain cell growth for many months. IL-4 acts differently on IC2 cells: the maximum level of DNA synthesis induced by IL-4 is always lower than that induced by IL-3 or GM-CSF and IL-4-induced proliferation is transient. IL-4, however, synergistically induced DNA synthesis of IC2 cells with limiting concentrations of IL-3 or GM-CSF. When IC2 cells were cultured with saturating concentrations of IL-3, GM-CSF or a combination of both, the doubling time was 25 +/- 1 h, whereas it decreased to 17 +/- 1 h when IL-4 was further added to the cultures. IAP reduced the DNA synthesis of IC2 cells induced by the above three growth factors. The doubling time of IC2 cells was 30 +/- 2 h when IC2 cells were cultured with sufficient concentrations of IL-3 in the presence of IAP. Cell cycle analysis revealed that the fraction of cells in Gl was decreased by IL-4 but was increased by IAP. TGF-beta also reduced IL-3-dependent DNA synthesis and increased the fraction of cells in Gl. The inhibitory effect on IL-3-dependent growth of IC2 cells was not increased when these cells were exposed simultaneously to TGF-beta and IAP. The results suggest that IL-3 and GM-CSF stimulate the growth of IC2 cells through similar pathways and that IL-4 augments the action of IL-3 or GM-CSF by decreasing the Gl period. It is also suggested that IAP and TGF-beta retard the growth of IC2 cells by increasing the fraction of cells in GI.
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PMID:Growth regulation of multi-factor-dependent myeloid cell lines: IL-4, TGF-beta and pertussis toxin modulate IL-3- or GM-CSF-induced growth by controlling cell cycle length. 268 Jan 12

Adenosine potentiates mouse bone marrow-derived mast cell mediator release by a mechanism that appears to involve cell surface adenosine receptors. In an attempt to explore possible interactions between G proteins and adenosine receptors, mast cells were incubated with activated pertussis toxin, an agent that ADP-ribosylates and inactivates some G protein subtypes, prior to challenge with specific antigen or the calcium ionophore A23187. Mast cells preincubated with 10 ng/ml pertussis toxin for at least 2 hr exhibited an inhibition of antigen-induced beta-hexosaminidase and leukotriene C4 release. The ability of adenosine to potentiate beta-hexosaminidase release was attenuated to an even greater degree by pertussis toxin. A23187-stimulated mediator release was not altered by pertussis toxin, although a modest inhibition of the ability of adenosine to enhance A23187-induced beta-hexosaminidase release was observed in pertussis toxin-treated mast cells. Although up to 24-hr exposure to 100 ng/ml pertussis toxin did not alter resting mast cell cyclic AMP levels, the ability of adenosine to elevate cell cyclic AMP concentrations was diminished markedly by doses of the toxin higher than those required to affect mediator release. Neither antigen-stimulated intracellular free calcium level augmentation alone nor the additional potentiation of these levels by adenosine was changed by pertussis toxin treatment. Inositol trisphosphate was generated by mast cells stimulated by IgE-mediated mechanisms, but a preincubation with pertussis toxin did not influence its generation. In summary, adenosine appeared to produce some of its alterations in mast cell biochemical events by a mechanism that was partially inhibited by pertussis toxin. The nature of the G protein linked to the mast cell adenosine receptor is yet to be determined.
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PMID:Alteration of mast cell responsiveness to adenosine by pertussis toxin. 284 50

High IgE responder rats were sensitized intraperitoneally with alum-adsorbed ovalbumin and Bordetella pertussis organisms. At day 0, 7, 14, 21 and 28 following sensitization the peritoneal cells were harvested and further processed for light and immunoelectron microscopical investigations using a specific anti-rat IgE immunogold sandwich method. The results obtained show that the number of peritoneal mast cells increase significantly during the course of sensitization. There is a time-dependent increase in the amount of immunogold particles on mast cell surfaces together with a shift of particle distribution towards the surface folds. Sensitized mast cells exhibit altered releasability as is indicated by slightly degranulated cells at day 21 and day 28 postsensitization. Additionally, about 25% of small lymphocytes which had entered the peritoneal cavity between day 7 and day 14 are heavily stained with the immunogold complex between day 14 and day 28 postsensitization. This is not so for macrophages (less than or equal to 0.2% positive cells) nor for eosinophils which do not show any staining activity at all despite they are present in high numbers.
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PMID:Time-course of IgE binding to rat peritoneal cells after sensitization with alum-adsorbed ovalbumin and Bordetella pertussis. 288 28

The effect of an additional adjuvant, Bordetella pertussis, on the clinical and histopathologic features of experimental autoimmune uveitis in black-hooded Lister rats was investigated. Disease was induced by a single footpad injection of purified retinal S-antigen in Freund's complete adjuvant. In those animals that did not receive B Pertussis the clinical features were those of a retinal vasculitis with disc edema, periphlebitis, and deep retinal infiltrates. In contrast, animals that received B pertussis developed lesions in the pigment epithelium and choroid. Histopathologic studies disclosed focal photoreceptor necrosis associated with mononuclear cell infiltration in both groups of animals. However, in the group that did not receive B pertussis the disease was predominantly a retinitis associated with perivascular infiltration of retinal vessels, whereas in the group that did receive B pertussis the main feature was a focal choroiditis, with superficial retinal lesions being rarely observed. Retinal photoreceptors were the target tissue in both groups of rats, but the route by which they were damaged was altered from predominantly retinal to choroidal by the addition of Bordetella pertussis as an adjuvant. This change may be ascribed to the ability of B pertussis toxin to sensitize vascular endothelium to local mast cell products, these cells being plentiful around choroidal vessels but absent in the retinal circulation.
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PMID:Differential effect of Bordetella pertussis on experimental posterior uveitis in the black-hooded Lister rat. 289 82

We have investigated the morphological effects of an intratracheal challenge with 50 micrograms ovalbumin (OA) on sensitized rat tracheas, in vivo. Female Sprague-Dawley rats were primed ten days before challenge with a single i.t. injection of 100 micrograms OA plus Bordetella pertussis (OA-BP). Two additional groups of animals served as controls: primed animals challenged with saline only and non-primed but OA-challenged animals. Sacrifices--and subsequent morphological studies--were performed prior to and 5, 15 and 60 min after challenge. At each time, the total numbers of epithelial nuclei, subepithelial mast cells (SEMC) and intraepithelial mast cells (IEMC) were scored in six non-adjacent cross sections per trachea. We found that: 1) priming with OA-BP alone did not induce any change in the tracheal mucosa with respect to morphological structure and mast cell counts; 2) no morphological change nor significant modification of the cell counts occurred at any time in tracheas from either of the control groups; 3) in contrast, a luminal heterogeneous exudate and a subepithelial oedema developed in 9 of the 15 tracheas of primed animals within 60 min of OA challenge. In those nine tracheas, the scores of intraepithelial nuclei, of IEMC and of SEMC were found to decrease significantly 15 min after challenge as compared with starting values (p less than 0.05 for each score). The decrease in the number of mucosal mast cells is probably related to the damages of the epithelial cells and to the difficulty with which depleted mast cells can be seen by toluidine blue staining.
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PMID:Morphological changes in rat tracheal mucosa immediately after antigen challenge. 289 14

The guanine nucleotide-binding proteins (G proteins), which transduce hormonal and light signals across the plasma membrane, are heterotrimers composed of alpha, beta, and gamma subunits. Activation of G proteins by guanine nucleotides is accompanied by dissociation of the heterotrimer: G + alpha.beta.gamma in equilibrium alpha G + beta.gamma. Brain contains several G proteins of which the most abundant are alpha 39.beta.gamma and alpha 41.beta.gamma. We have used proteolysis by trypsin to study the functional domains of the alpha subunits. In the presence of guanosine 5'-(3-O-thio)triphosphate, trypsin removes a 2-kDa peptide from the amino terminus of these proteins (Hurley, J. B., Simon, M. I., Teplow, D. B., Robishaw, J. D., and Gilman, A. G. (1984) Science 226, 860-862; Winslow, J. W., Van Amsterdam, J. R., and Neer, E. J. (1986) J. Biol. Chem. 261, 7571-7579). Tryptic cleavage does not affect the GTPase activity of the truncated molecule nor the apparent Km for GTP. However, removal of the 2-kDa amino-terminal peptide prevents association of the alpha subunits with beta.gamma. Since the apparent substrate for pertussis toxin-catalyzed ADP-ribosylation is the alpha.beta.gamma heterotrimer, the trypsin-cleaved alpha subunit is not a substrate for the toxin. Digestion of the carboxyl terminus of alpha 39 with carboxypeptidase A prevents ADP-ribosylation by pertussis toxin but does not interfere with the formation of alpha 39.beta.gamma heterotrimers. We do not yet know whether the amino-terminal region of alpha 39 interacts with beta gamma directly or whether it is necessary to maintain a conformation of alpha 39 which is required for heterotrimer formation. Further studies are needed to define the nature of the contracts between alpha and beta gamma subunits since understanding the structural basis for their reversible interaction is fundamental to understanding their function.
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PMID:The amino terminus of G protein alpha subunits is required for interaction with beta gamma. 313 54

Experimental autoimmune uveoretinitis (EAU) is an ocular autoimmune disease induced in rats by immunization with retinal S-antigen. Athymic nude rats (rnu/rnu) have been previously shown to be refractory to EAU induction and antibody production to S-antigen, while heterozygous (rnu/+) are good responders. Increasing the antigen dose and adding pertussis adjuvant produced ocular disease in some nude rats, and antibody response in most of them. Specific IgE antibodies were demonstrated by ELI-SA only in the serum of nude rats presenting the disease. However, most immunized nude rats had evidence of mast cell sensitization to S-antigen (direct degranulation test) and of circulating specific IgE detected by passive sensitization of normal mast cells (indirect degranulation test). This positive response could be explained by an incomplete depletion of the different T lymphocyte subsets.
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PMID:Experimental autoimmune uveoretinitis in athymic rats: specific IgE response to retinal S-antigen and disease. 387 39


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