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)

The skin sites of the mouse where delayed-type hypersensitivity (DTH) reactions are most easily elicited (foot pads and ears) are particularly rich in 5-hydroxytryptamine (5-HT)-containing mast cells. Since mice are deficient in circulating basophils, which play a role in at least some DTH reactions, we investigated the possibility that the mast cells were playing an important role in the evolution of the skin reactions of DTH in mice. We found that reserpine, a drug which depletes mast cells of 5-HT, abolished the ability of the mouse to make DTH reactions in the skin. The suppressive effect of reserpine could be partially blocked by monoamine oxidase inhibitors which prevent the degradation of 5-HT in the cytosol of the mast cell. Spleen cells of immune, reserpine-treated mice transferred DTH reactions to nonimmune mice normally, indicating that the reserpine treatment did not affect immune T cells. DTH reactions could not be transferred into reserpine-treated mice. We suggest that T cells are continually emigrating from the blood, through postcapillary venule endothelium, by a mechanism which does not depend on vasoactive amines. If they are appropriately immune and meet the homologous antigen in the tissue, they induce mast cells to release vasoactive amines which cause postcapillary venule endothelial cells to separate, allowing the egress from the blood of cells which ordinarily do not recirculate. The secondarily arriving vasoactive amine-dependent cells are responsible for the micro- and macroscopic lesions of DTH reactions. Chemotactic factors may also be involved in bringing cells to the DTH reaction sites but we propose that T-cell regulation of vasoactive amine-containing cells allows the effector cells to pass through the endothelial gates after they are called.
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PMID:Requirement for vasoactive amines for production of delayed-type hypersensitvity skin reactions. 116 73

The in vitro production of histamine releasing factor (HRF) by lymphoid cells of rats, both normal and infected with Nippostrongylus brasiliensis, has been studied. Spleen cells and thymocytes were cultured either alone or in the presence of mitogen (PHA, 10 and 50 micrograms/ml) and the dialysed cell-free supernatants were tested for histamine releasing activity on rat peritoneal and pleural mast cell in vitro. We found that spleen cells and thymocytes of normal rats stimulated with PHA in 24 h cultures generated a factor which released histamine and 5-hydroxytryptamine from mast cells, and this ability was potentiated following N. brasiliensis infection of rats - lymphoid cells donors. Pleural mast cells were more sensitive to the action of HRF than peritoneal cells. Rat HRF had an apparent m.w. of 50,000 to 70,000 daltons as determined by gel chromatography and was a heat stable protein inducing histamine release from homologous mast cells in a very rapid (complete in 1-2 min at 37 degrees C), dose and temperature dependent secretory process.
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PMID:Rat lymphoid cell--derived histamine and 5-hydroxytryptamine releasing factor. 128 Apr 98

The effects of IPD-1151T (suplatast tosilate), a novel anti-allergic drug, on murine mast cell induction were examined by the in vitro cell culture technique. Spleen cells from BALB/c mice suspended in RPMI-1640 medium containing interleukin 3 were cultured in the presence or absence of IPD-1151T. Half the volume of the medium was changed every 4 days. Mast cell numbers increased as the culture time went on and reached a peak on the 16th day, when spleen cells were cultured without IPD-1151T. However, induction of mast cells from spleen cell cultures was inhibited by IPD-1151T in a dose dependent fashion. These results strongly suggest that IPD-1151T is a very useful agent for therapy in allergic diseases.
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PMID:[Inhibitory effect of IPD-1151T (suplatast tosilate) on mast cell induction from normal mouse spleen cells]. 133 62

Interstitial cystitis is an inflammatory disease of unknown etiology. To facilitate the study of the pathophysiology of interstitial cystitis, an animal model that correlates with the clinical features of interstitial cystitis and expresses histologic features consistent with those observed in interstitial cystitis patients was developed. Various strains of mice were immunized with a syngeneic bladder homogenate to determine their susceptibility to the induction of autoimmune cystitis. Of 3 mouse strains tested, only the Balb/cAN mice reproducibly developed the clinical correlates and histological features consistent with those observed in interstitial cystitis. In a blinded pathologic review, autoreactive Balb/cAN bladders were correctly distinguished from chronic bacterial cystitis, sham treated bladders and normal control bladders. Edema, fibrosis, perivascular lymphocytic infiltrations and detrusor mast cell accumulation were apparent in 75% of the Balb/cAN mice 2 weeks after immunization and 100% at 4 weeks. These histologic features plateaued and remained stable for at least 6 months. Grossly, the immunized mouse bladders were fibrotic and contracted with a significantly (p < .05) decreased fluid capacity. On hydrodistension, increased vascular prominence and petechial hemorrhage (glomerulations) were evident. Instillation of 14C-urea demonstrated increased permeability in immunized bladders compared with controls. A cellular autoimmune basis for the cystitis is supported by adoptive transfer studies. Spleen cells from experimental mice but not controls transferred the histological features of the disease to naive mice. These studies outline the development of a new experimental autoimmune cystitis model that expresses features similar to those frequently observed in human interstitial cystitis, and may provide a model for the study of the inflammatory process associated with interstitial cystitis. Furthermore, these data suggest a possible role for cellular immune components in interstitial cystitis.
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PMID:Experimental autoimmune cystitis: a potential murine model for ulcerative interstitial cystitis. 143 51

The kinetics and quality of the alloimmune reaction were studied in CBA (H-2k) mice treated for passive enhancement of tumor allografts (Sa 1 indigenous of A/J (H-2a or H-2k/d) mice). Serum samples of treated animals were tested for their biological properties relevant to different antibody isotypes in vitro (hemagglutination, complement-dependent cytotoxicity, and anaphylaxis, i.e., mast cell degranulation involving all main Ig isotypes; IgM, IgG2, and IgG1, IgE, respectively) as well as in vivo (allograft enhancement). Spleen cells from these treated animals were examined for their capacity to interfere with the rejection of tumor allografts by adoptive transfers into syngeneic recipients. In vitro, 51Cr release cytolysis assays were performed in order to test their cytolytic and regulatory activities in comparison to rejecting control animals. It has been shown that: grafted mice, pretreated for passive enhancement, kept their grafts longer and synthetized anaphylactic antibodies (mainly IgG1) earlier and at higher titers than normal serum controls, which rejected the same Sa 1 allografts. Mice with enhanced tumors synthetized cytotoxic antibodies (mainly IgG2) later than rejecting controls. Serum samples from treated and control animals, harvested 10 days (early sera) and 30 days (late sera) after grafting, were injected with a "normal dose" (0.2 ml) and a "high" dose (0.4 ml) to new CBA recipients grafted with Sa 1. Early immune sera were only enhancing at high doses when derived from animals previously treated for enhancement (at the low dose both immune sera were enhancing). Late sera, presenting both complement-fixing, cytotoxic (predominantly IgG2), and IgG1 anaphylactic alloantibodies in the two groups, induced enhancement in all cases, but more strongly when derived from the group treated for Sa 1 enhancement. Adoptive transfer of spleen cells from animals treated for passive enhancement were able either to inhibit the accelerated rejection (Day 10) or to promote enhancement of Sa 1 allogeneic cells (Day 30) while similar cells taken (Day 10 and Day 30) from control graft-rejecting mice transferred accelerated rejection. Among the transferred T-cell sub-populations, the suppressive effect was mediated by Lyt 2 T cells. In vitro, these spleen cells showed a weaker cytolytic activity than those of allograft-rejecting mice. Moreover, they were able to regulate the cytolytic activity of cytotoxic effector cells from specifically immunized CBA mice.
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PMID:Evolution of alloantibodies and suppressor cells in allografted mice treated for passive enhancement. 402 70

Spleen cells from Nippostrongylus brasiliensis-infected mice produce large amounts of histamine in response to adult worm antigen. This phenomenon results from the production of HCSF (histamine-producing cell-stimulating factor, probably related to IL3) by sensitized lymphocytes. This factor acts on its target cells (presumably mast cell precursors) by inducing a rapid increase in histamine synthesis. Similarly, parasite infection generates enhanced histamine production by spleen cells in response to concanavalin A (Con A). This results from increases in both HCSF production and the HCSF sensitivity of its target cells. In all cases, maximal histamine and HCSF productions are obtained on day 8 after infection and coincide with parasite rejection. Methyl prednisolone suppresses HCSF production by infected mouse spleen cells in response to worm antigen or Con A. HCSF activity is found in vivo on day 8 in the sera of infected mice, 4 h after they are challenged with an i.v. injection of adult worm antigen. No activity is detected in the sera of normal mice with or without antigen injection. Sera from infected mice that did not receive the antigen exhibit a slight HCSF activity on day 8. Our data bring the first evidence of the existence of an in vivo production of HCSF.
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PMID:In vitro and in vivo histamine-producing cell-stimulating factor (or IL3) production during Nippostrongylus brasiliensis infection: coincidence with self-cure phenomenon. 619 4

Hexachlorobenzene (HCB) is a persistent environmental pollutant with toxic effects in man and rat. Reported adverse effects are hepatic porphyria, neurotoxicity, and adverse effects on the reproductive and immune system. To obtain more insight into HCB-induced mechanisms of toxicity, we studied gene expression levels using DNA microarrays. For 4 weeks, Brown Norway rats were fed a diet supplemented with 0, 150, or 450 mg HCB/kg. Spleen, mesenteric lymph nodes (MLN), thymus, blood, liver, and kidney were collected and analyzed using the Affymetrix rat RGU-34A GeneChip microarray. Most significant (p < 0.001) changes, compared to the control group, occurred in spleen, followed by liver, kidney, blood, and MLN, but only a few genes were affected in thymus. This was to be expected, as the thymus is not a target organ of HCB. Transcriptome profiles confirmed known effects of HCB such as stimulatory effects on the immune system and induction of enzymes involved in drug metabolism, porphyria, and the reproductive system. In line with previous histopathological findings were increased transcript levels of markers for granulocytes and macrophages. New findings include the upregulation of genes encoding proinflammatory cytokines, antioxidants, acute phase proteins, mast cell markers, complements, chemokines, and cell adhesion molecules. Generally, gene expression data provide evidence that HCB induces a systemic inflammatory response, accompanied by oxidative stress and an acute phase response. In conclusion, this study confirms previously observed (immuno)toxicological effects of HCB but also reveals several new and mechanistically relevant gene products. Thus, transcriptome profiles can be used as markers for several of the processes that occur after HCB exposure.
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PMID:Toxicogenomics of subchronic hexachlorobenzene exposure in Brown Norway rats. 1515 7

Warifteine is a bisbenzylisoquinoline alkaloid isolated from the Cissampelos sympodialis Eichl (Menispermaceae). This plant is used in the folk medicine for the treatment of airway respiratory diseases. A murine model of immediate allergic reaction was used to evaluate warifteine treatment in the IgE production, leukocyte activation, thermal hyperalgesia, mast cell degranulation and scratching behavior. BALB/c mice treated with warifteine (0.4-10 mg/Kg) 1 h before OVA sensitization reduced OVA induced paw edema as well as the OVA-specific IgE serum titers as compared with non-treated and OVA-sensitized animals. Warifteine also reduced the mice death evoked by IgE-dependent anaphylactic shock reaction at 30 min after intravenous OVA challenge. To assess the effect of warifteine treatment on T cell proliferative response, spleen cells from warifteine treated or non-treated and OVA-sensitized animals were evaluated. Spleen cells from warifteine treated animals (2.0 mg/kg) did not proliferate following OVA stimulation as compared with spleen cell cultures from non-treated animals. This response may be related with the increase of NO production as observed in peritoneal macrophage cultures treated with warifteine. Thermal hyperalgesia evoked by IgE or histamine/5-hydroxytryptamine challenge was inhibited on rats at dose of 4.0 mg/kg. Warifteine treatment (0.6 or 6.0 microg/ml) also decreased the IgEalphaDNP-BSA sensitized mast degranulation after DNP-BSA challenge measured by histamine release. In addition, compound 48/80-induced scratching behavior was also sensitive to warifteine treatment. These results demonstrate for the first time that warifteine treatment reduced the allergy-associated responses.
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PMID:Warifteine, a bisbenzylisoquinoline alkaloid, decreases immediate allergic and thermal hyperalgesic reactions in sensitized animals. 1832 42

The aim of the study is to evaluate clinical features, treatments and outcome of patients with systemic mast cell disease (MCD) who arrived to the attention of hematologists. A retrospective study was conducted over 1995-2006 in patients admitted in 18 Italian hematological divisions. Twenty-four cases of advanced MCD were collected: 12 aggressive SM (50%), 8 mast cell leukemia (33%), 4 SM with associated clonal non-mast cell-lineage hematologic disease (17%). Spleen and liver were the principal extramedullary organ involved. The c-kit point mutation D816V was found in 13/18 patients in which molecular biology studies were performed (72%). Treatments were very heterogeneous: on the whole Imatinib was administered in 17 patients, alpha-Interferon in 8, 2-CdA in 3; 2 patients underwent allogeneic hematopoietic stem cell transplantation. The overall response rate to Imatinib, the most frequently employed drugs, was of 29%, registering one complete remission and four partial remission; all responsive patients did not present D816V c-kit mutation. Overall three patients (12%) died for progression of disease. We conclude that MCD is characterized by severe mediator-related symptoms but with a moderate mortality rate. D816V c-kit mutation is frequent and associated with resistance against Imatinib. Because of the rarity of these forms, an effective standard of care is lacking. More data are needed to find new and successful therapeutic strategies.
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PMID:Advanced mast cell disease: an Italian Hematological Multicenter experience. 1903 14

Grifola gargal Singer, a medicinal mushroom, has been found to be effective for the prevention and treatment of various chronic inflammatory diseases. However, the effects of G. gargal on allergic diseases are unknown. The present study investigated the effect of G. gargal extract on allergic bronchial asthma. Asthma was induced in mice by ovalbumin sensitization and inhalation. The grade of asthma was compared between mice fed with chow containing G. gargal extract and mice given standard chow. The human mast cell and eosinophilic cell lines were used for in vitro studies. G. gargal extract significantly reduced airway hyperresponsiveness, lung eosinophilic infiltration, lung interleukin (IL)-13 expression, and plasma IgE level and significantly increased IL-10 plasma levels compared to untreated control mice. Spleen regulatory T cells were significantly increased in mice treated with the G. gargal extract compared with untreated control mice. G. gargal extract significantly suppressed expression of cytokines in mast cells and eosinophils compared with control cells. Overall, these observations show that G. gargal extract augments the lung population of regulatory T cells and ameliorates allergic inflammation and airway hyperresponsiveness in mice with allergic bronchial asthma, suggesting the potential therapeutic benefit of G. gargal extract in allergic diseases.
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PMID:The Medicinal Mushroom, Grifola gargal, Ameliorates Allergic Bronchial Asthma. 2926 Oct 8


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