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)

Amiodarone, a promising drug for the treatment of tachyarrythmias, was recently found to have immunomodulatory effects in vitro. We hypothesized that amiodarone would affect the immune system in vivo and examined the effect of amiodarone on myocarditis in rats. We induced experimental autoimmune myocarditis in rats by cardiac myosin immunization and treated the animals with an intraperitoneal injection of amiodarone at 25 mg/kg/every other day, 10 times after the induction of experimental autoimmune myocarditis. In the treated group, both microscopic and macroscopic examinations showed reduced heart weights, a mild and localized infiltration of inflammatory cells and fibrosis in the myocardium, and a mild congestion in the liver and lungs as compared with the control group. The phenotypic distribution of lymphocytes in peripheral blood showed a significant decrease in the CD4/CD8a ratio in the treated group, but not in the control group. The proportion of mast cells involved in inflammatory cell infiltration was lower in the treated group than the control group. In vitro, amiodarone inhibited the proliferation of mast cells by arresting them in the G2 phase of the cell cycle. These results indicated that amiodarone minimized the progression of experimental autoimmune myocarditis, suggesting a potential therapeutic role for amiodarone treatment in patients suffering from myocarditis, especially myocarditis complicated by cardiac arrhythmias. One possible mechanism by which amiodarone minimizes the progression of experimental autoimmune myocarditis may be to affect the immune system via the immunomodulatory effects on T cell and mast cell functions.
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PMID:Amiodarone minimizes experimental autoimmune myocarditis in rats. 1278 99

The killer cell lectin-like receptor G1 (KLRG1) is the mouse homologue of the rat mast cell function-associated Ag and contains a tyrosine-based inhibitory motif in its cytoplasmic domain. It has been demonstrated that KLRG1 is induced on activated NK cells and that KLRG1 can inhibit NK cell effector functions. In this study, we show that in naive C57BL/6 mice KLRG1 is expressed on a subset of CD44(high)CD62L(low) T cells. KLRG1 expression can be detected on a small number of V(alpha)14i NK T cells but not on CD8alphaalpha(+) intraepithelial T cells that are either TCRgammadelta(+) or TCRalphabeta(+). We also show that KLRG1 expression is dramatically induced on approximately 50% of the CD8(+) T cells during both a viral and a parasitic infection. Interestingly, during Toxoplasma gondii infection, KLRG1 is up-regulated on CD4(+) T cells. Although KLRG1 expression can be induced on both NK cells and T cells, the molecular mechanism leading to the induction of KLRG1 differs in these two subsets of cells. Indeed, the up-regulation of KLRG1 on NK cells can be driven in vivo by cytokines, whereas KLRG1 cannot be induced on CD8(+) T cells by cytokines. In addition, although induction of KLRG1 on T cells appears to require TCR engagement in vivo, TCR engagement is not sufficient for KLRG1 induction in vitro. Taken together, these data suggest that the expression and induction of KLRG1 on T cells are tightly regulated. This could have important biological consequences on T cell activation and homeostasis.
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PMID:Differential regulation of killer cell lectin-like receptor G1 expression on T cells. 1279 13

Two novel stem cell factor (SCF) dependent human mast cell lines, designated LAD 1 and 2, were established from bone marrow aspirates from a patient with mast cell sarcoma/leukemia. LAD 1 and 2 cells have the ultrastructural features of human mast cells, and express FcepsilonRI, CD4, 9, 13, 14, 22, 31, 32, 45, 64, 71, 103, 117, 132, CXCR4 (CD184), CCR5 (CD195); and intracytoplasmic histamine, tryptase and chymase. LAD 1 and 2 do not exhibit activating mutations at codon 816 of c-kit. Both LAD 1 and 2 release beta-hexosaminidase following FcepsilonRI or FcgammaRI aggregation. The availability of these cell lines offers an unparalleled circumstance to examine the biology of human mast cells.
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PMID:Characterization of novel stem cell factor responsive human mast cell lines LAD 1 and 2 established from a patient with mast cell sarcoma/leukemia; activation following aggregation of FcepsilonRI or FcgammaRI. 1280 24

While severe protein energy malnutrition (PEM) has been known to depress several immune functions, allergies are suppressed by decreasing IgE and impairing vascular permeability and mast cell functions. To address the effect of moderate protein malnutrition without growth arrest and protein hypernutrition on type I allergy, we examined the effect of various levels of protein nutrition on allergy at humoral immunity and the regulation of Th cell function levels. Mice fed 100 g/kg (moderate protein malnutrition; MPM), 200 g/kg (normal protein nutrition; PN) and 400 g/kg (protein hypernutrition; PH) protein diets were intraperitoneally sensitized to ovalbumin (OVA) in aluminum hydroxide. Higher elevations of OVA-specific IgE and total IgE in the serum were observed in the PH group as compared to the PN group. However, OVA-specific IgE in the MPM group was not significantly different from that in the PN group, although the former appeared higher than the latter. While CD3, CD4, CD8 and B220 expressions in the splenic lymphocytes were decreased in the MPM group, B220 expressions were increased in the PH group. Splenic lymphocyte proliferative responses to OVA were augmented in the PH group and depressed in the MPM group. IFN-gamma production from splenic lymphocytes was significantly decreased; however, IL-4 production was not affected significantly in the MPM group, and increased in the PH group. These findings suggest that immune functions to specific antigens in the MPM state are depressed at the cytokine level but not in terms of IgE responses. They also suggest that immune functions become Th2-predominant in the PH state, resulting in an increased risk of type I allergy.
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PMID:IgE responses in mice fed moderate protein deficient and high protein diets. 1295 95

Contact hypersensitivity (CHS) induced by a hapten is thought to be mediated by T helper type 1 (Th1) cells. However, FITC can induce contact allergy in vivo, and in vitro studies suggest that this response is Th2-type driven. We compared CHS reactions induced by FITC or dinitrofluorobenzene (DNFB), a well-known Th1 inducing hapten, in Balb/c mice, C57/B6 mice, and several gene knock-out mice, and investigated the role of Th1/Th2 cytokines, T cell populations, eosinophils, and mast cells. Balb/c mice (Th2 dominant strain) had a stronger response to FITC than C57/B6 mice (Th1 dominant strain). The skin inflammation was characterized by edema and eosinophilia, and serum IgE levels were elevated following FITC challenge. All responses were enhanced by a second round of sensitization. Anti-TNF-alpha or anti-very late antigen-4 (VLA-4) antibody partly inhibited both FITC- and DNFB-induced CHS. Pretreatment of mice with anti-IL-4 antibody, anti-IL-5 antibody, recombinant INF-gamma, or the mast-cell depleting agent 48/80 significantly diminished edema formation, and Stat6(-/-) mice were fully protected from FITC-induced CHS, while DNFB-induced CHS was enhanced (Stat6(-/-), mast cell depletion) or not affected (anti-IL-5 antibody). Further, mice lacking CD4(+) T cells and mice lacking both CD8 and MHC II showed very little reaction at all to FITC, while the absence of CD8 T cells alone or MHC II alone conferred partial protection only. These findings indicate a contribution of MHC II-independent CD4(+) T cells and/or CD4(+) NKT cells to the Th2 response triggered by FITC in vivo, and makes FITC-induced CHS a suitable animal model for atopic dermatitis.
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PMID:Essential role of MHC II-independent CD4+ T cells, IL-4 and STAT6 in contact hypersensitivity induced by fluorescein isothiocyanate in the mouse. 1509 84

Hypersensitivity Pneumonitis (HP) is an immunologically mediated interstitial lung disease that may result from repeated inhalation of many different environmental agents. Heterogeneity of the clinical presentation and bronchoalveolar lavage profiles have been described, possibly related to different occupational exposures. The aim of our study was to compare bronchoalveolar lavage fluid (BALF), clinical, functional and radiological characteristics of the two most frequent forms of HP seen in our practice: Suberosis (an HP related to moldy cork dust exposure) and bird fancier's disease (BFD). We included 81 patients with Suberosis, with a mean age of 38.8 +/- 11.3 years and a mean exposure of 20.0 +/- 10.5 years and 32 patients with BFD, with a mean age of 46.3 +/- 11.8 years and mean exposure of 10.5 +/- 1.0 years. Patients with BFD had more acute forms, while subacute and chronic presentations predominated in Suberosis. Restrictive defect was the most frequent pattern of lung function impairment, and more severe in BFD. Ground glass opacities were the most frequent pattern in high-resolution computed tomography. A normal chest x-ray was more frequently seen in Suberosis. Both types of HP had lymphocytic alveolitis in BALF: Suberosis - 6.6 +/- 5.7 x 10(5) ml-l cells, 58.8 +/- 18.9% lymphocytes; bird fancier's disease - 9.0 +/- 6.5 x 105 ml-l cells, 61.7 +/- 22.2% lymphocytes. Although BALF CD8+ lymphocytes predominated in both diseases, the proportion of CD4+ and CD4/CD8 ratios were significantly higher in bird fancier's disease (Suberosis: 0.47 +/- 0.33 versus BFD: 1.1 +/- 1.5; p < 0.005). Moreover, BALF cellularity and mast cell counts were also significantly higher in BFD. In conclusion, Suberosis and bird fancier's disease are HP with different clinical and laboratory profiles, suggesting that despite their pathophysiological similarities, different antigenic exposures may cause different immune and inflammatory response dynamics in the lung.
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PMID:Suberosis and bird fancier's disease: a comparative study of radiological, functional and bronchoalveolar lavage profiles. 1516 Apr 39

Extrinsic Allergic Alveolitis (EAA) is an immunologically mediated interstitial lung disease that may result from repeated inhalation of many different environmental agents. Heterogeneity of the clinical presentation and bronchoalveolar lavage profiles has been described, possibly related to different occupational exposures. The aim of our study was to compare bronchoalveolar lavage fluid (BALF), clinical, functional and radiological characteristics of the two most frequent forms of EAA seen in our practice: Suberosis and Bird Fancier's Disease (BFD). We included 81 patients with Suberosis, with a mean age of 38.8+/-11.3 years and a mean exposure of 20.0 +/- 10.5 years and 32 patients with BFD, with a mean age of 46.3+/-11.8 years and mean exposure of 10.5 +/- 1.0 years. Patients with BFD had more acute forms, while subacute and chronic presentations predominated in Suberosis. Restrictive defect was the most frequent pattern of lung function impairment, and more severe in BFD. Ground glass opacities were the most frequent pattern in high-resolution computed tomography. A normal chest x-ray was more frequently seen in Suberosis. Both types of EAA had lymphocytic alveolitis in BALF: Suberosis - 6.6 +/- 5.7 x 105 ml-1 cells, 58.8 +/- 18.9% lymphocytes; bird fancier's disease - 9.0 +/- 6.5 x 105 ml-1 cells, 61.7 +/- 22.2% lymphocytes. Although BALF CD8+ lymphocytes predominated in both diseases, the proportion of CD4+ and CD4/CD8 ratios were significantly higher in Bird Fancier's Disease (Suberosis: 0.47 +/- 0.33 versus BFD: 1.1 +/- 1.5; p <0.005). Moreover, BALF cellularity and mast cell counts were also significantly higher in BFD. In conclusion, Suberosis and bird fancier's disease are EAA with different clinical and laboratory profiles, suggesting that despite their pathophysiological similarities, different antigenic exposures may cause different immune and inflammatory response dynamics in the lung.
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PMID:[Suberosis and bird fancier's disease: comparative study of radiological, functional and bronchoalveolar characteristics profile]. 1519 Apr 28

Specific allergen injection immunotherapy is highly effective in IgE-mediated diseases, such as allergic rhinitis and venom anaphylaxis. Immunotherapy inhibits both early and late responses to allergen exposure. Immunotherapy is accompanied by increases in allergen-specific IgG, particularly the IgG4 isotype, which blocks not only IgE-dependent histamine release from basophils but also IgE-mediated antigen presentation to T cells. Immunotherapy acts on T cells to modify peripheral and mucosal T(H)2 responses to allergen in favor of T(H)1 responses. Recent studies have identified increased IL-10 production in peripheral blood and mucosal surfaces after immunotherapy. IL-10 has numerous potential antiallergic properties, including suppression of mast cell, eosinophil, and T-cell responses, as well as acting on B cells to favor heavy chain class switching to IgG4. These IL-10-producing cells might be so-called regulatory T cells and appear to be identified by the CD4(+)CD25(+) phenotype. Studies in mice suggest that dendritic cells play a vital role in induction of regulatory T cells. Novel approaches to immunotherapy currently being explored include the use of adjuvants, such as monophosphoryl lipid A or nucleotide immunostimulatory sequences derived from bacteria that potentiate T(H)1 responses. Alternative strategies include the use of allergen-derived peptides or modified recombinant allergen vaccines that act on T cells while minimizing the IgE-dependent mast cell activation that is dependent on the native allergen conformation.
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PMID:Mechanisms of immunotherapy. 1520 78

HIV-1 infection leads to a disease that attacks the central regulatory mechanisms of the immune response. As mucosal tissue is one of the primary sites infected with HIV in vivo, we examined the effects of HIV exposure on human mast cells, important components of mucosal defense. Using the human mast cell line, HMC-1, which expresses CXCR4 but not CCR5 on the cell surface, we found that several HIV-1 X4 tropic lab (IIIB, RF) and primary isolates but not R5 (BAL, ADA) isolates productively infected these cells. Furthermore, stem cell factor-dependent mast cells derived from primary fetal liver or cord blood cultures were also productively infected with both X4 and R5 HIV-1 strains. Infection was blocked at the level of viral entry using monoclonal antibodies to CXCR4 and CD4. Treatment of HMC-1 with TNF-alpha and TGF-beta stimulated cell surface expression of CCR5 and up-regulated expression of both CCR5 and CXCR4 on primary mast cells, leading to increased susceptibility to both X4 and R5 viral isolates. HIV-1 infection also resulted in histamine release from these mast cells, most due in part to HIV-mediated cell death. These results demonstrate that X4 viruses can use CD4 and the CXCR4 receptor to infect mast cells, suggesting that mast cell-T cell interactions may contribute to HIV mediated immune dysfunction in the mucosa.
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PMID:Alterations in mast cell function and survival following in vitro infection with human immunodeficiency viruses-1 through CXCR4. 1559 22

Stress, defined as an acute threat to homeostasis, evokes an adaptive or allostatic response and can have both a short- and long-term influence on the function of the gastrointestinal tract. The enteric nervous system is connected bidirectionally to the brain by parasympathetic and sympathetic pathways forming the brain-gut axis. The neural network of the brain, which generates the stress response, is called the central stress circuitry and includes the paraventricular nucleus of the hypothalamus, amygdala and periaqueductal gray. It receives input from the somatic and visceral afferent pathways and also from the visceral motor cortex including the medial prefrontal, anterior cingulate and insular cortex. The output of this central stress circuit is called the emotional motor system and includes automatic efferents, the hypothalamus-pituitary-adrenal axis and pain modulatory systems. Severe or long-term stress can induce long-term alteration in the stress response (plasticity). Corticotropin releasing factor (CRF) is a key mediator of the central stress response. Two CRF receptor subtypes, R1 and R2, have been described. They mediate increased colonic motor activity and slowed gastric emptying, respectively, in response to stress. Specific CRF receptor antagonists injected into the 0 block these visceral manifestations of stress. Circulating glucocorticoids exert an inhibitory effect on the stress response by receptors located in the medial prefrontal cortex and hippocampus. Many other neurotransmitters and neuroimmunomodulators are being evaluated. Stress increases the intestinal permeability to large antigenic molecules. It can lead to mast cell activation, degranulation and colonic mucin depletion. A reversal of small bowel water and electrolyte absorption occurs in response to stress and is mediated cholinergically. Stress also leads to increased susceptibility to colonic inflammation, which can be adaptively transferred among rats by sensitized CD4(+) lymphocytes. The association between stress and various gastrointestinal diseases, including functional bowel disorders, inflammatory bowel disease, peptic ulcer disease and gastroesophageal reflux disease, is being actively investigated. Attention to the close relation between the brain and gut has opened many therapeutic avenues for the future.
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PMID:Stress and the gastrointestinal tract. 1574 Apr 74


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