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

The evidence reviewed here indicates that the eosinophil has the ability to kill many species of helminths and likely does so during worm infection. This toxic ability appears to be regulated by several other cells including mast cells, monocytes, and T lymphocytes. Eosinophils kill helminths through their ability to generate potent oxidants and through their content of cationic proteins, which likely achieve high concentrations at points of granule deposition. Eosinophils also participate in inflammation in human disease especially asthma, skin diseases, and heart disease. Though present concepts hold that the mast cell is the cornerstone of the allergic inflammatory response (450), the findings that eosinophils bind IgE and are activated by antigen-IgE complexes and that the eosinophil can elaborate many inflammatory mediators raise the possibility that the eosinophil might also be involved in the initiation of inflammatory responses. Finally, an eosinophil-related protein appears to play an undefined role in human reproduction.
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PMID:The eosinophilic leukocyte: structure and function. 353 19

Problems of arrhythmogenic sudden death (ASD) in athletes have been re-assessed on the clinicopathological plane, encompassing the emerging, unsolved, question of so-called idiopathic ventricular tachycardia, and its debated diagnostics versus arrhythmogenic right ventricular dysplasia-cardiopathy. Ischemic-infarction ASD from coronary artery pathology in young athletes has been seen to present with atherosclerotic "soft" subintimal plaques, rich in newly formed smooth myocytes, often attended by adventitial mast cell, as suspect microscopic markers of spasm, relevant to reperfusion; these features can be found also in precociously intramural arteries, responsible for ASD. Rare congenital abnormalities of the coronary ostia occasionally underlie ASD, together with the acquired aneurysmic coronaritis of chronic Kawasaki disease. Ischemic ASD can also be due to coronary arteriolopathy attending hypertrophic cardiomyopathy, a not uncommon disease in athletes, to be carefully discriminated from training heart hypertrophy. Young South-American sportsmen with Chagas' chronic cardiopathy seem to be at particular risk of ASD. Minor, but specific arrhythmogenic cardiac malformations such as accessory AV pathways have been detected in athletes succumbing to otherwise unexplained ASD, undergone careful post-mortem investigation. The need of more attentive and extended histopathologic control emerges from the hitherto ignored cardiac neuropathological substrates of reflexogenic ASD, which is cogent to problems of ASD in competing athletes. The thorough examination of the cardiac vascular centers in the brain stem, and of the peripheral cardiac innervation, at either abutments of the arc of dive- and/or Bezold-Jarisch cardioinhibitory-vasodepressor reflex, made it possible to suggest novel clinicopathological explanations in controversial cases of athletes' ASD, safeguarding from grave leval misjudgements due to sport's forensic medical mistakes.
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PMID:Structural and non-structural disease underlying high-risk cardiac arrhythmias relevant to sports medicine. 750 Jun 31

Adjuvants historically are considered to stimulate immune responses 'non-specifically'. Recently, a renewed understanding of the critical role of innate immunity in influencing the development of an adaptive immune response has led researchers to a better understanding of 'the adjuvant effect'. Although innate immune cells do not respond to specific antigenic epitopes on pathogens, they do produce restricted responses to particular classes of pathogens via pattern recognition receptors such as Toll-like receptors (TLR). Coxsackievirus infection was found to upregulate TLR4 on mast cells and macrophages immediately following infection. Although both susceptible and resistant mice produce a mixture of Th1 and Th2 cytokines, susceptible mice have increased levels of key proinflammatory cytokines, increased numbers of mast cells, and go on to develop chronic autoimmune heart disease. TLR4 signalling also increases acute myocarditis and proinflammatory cytokines in the heart. Many similarities are described in the pathogenesis of Coxsackievirus and the adjuvant-induced model of myocarditis including upregulation of particular TLRs and cytokines soon after inoculation. Recent findings suggest that mast cell activation by viruses or adjuvants may be important in initiating autoimmune disease.
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PMID:Viruses as adjuvants for autoimmunity: evidence from Coxsackievirus-induced myocarditis. 1538 90

There are fundamental differences between males and females with regard to susceptibility to heart disease. Although numerous animal models of heart failure have demonstrated that premenopausal females are afforded cardioprotection and, therefore, fare better in the face of cardiac disease than their male counterparts, many questions as to how this occurs still exist. Recently, we showed that 1) increased mast cell density is associated with adverse ventricular remodeling and 2) chemically induced mast cell degranulation using compound 48/80 resulted in remarkable changes in matrix metalloproteinase (MMP) activity, cardiac collagen structure, and cardiac diastolic function in normal male rats. With the known gender differences in cardiac disease in mind, we sought to examine the effects of chemically induced cardiac mast cell degranulation in isolated, blood-perfused hearts of intact female rats, ovariectomized female rats, and ovariectomized female rats treated with 17beta-estradiol. In response to mast cell degranulation, no significant differences in cardiac function, MMP-2 activity, or collagen volume fraction were observed between intact female rats and ovariectomized female rats treated with estrogen. In the ovariectomized female group, a significant rightward shift in the left ventricular pressure-volume relation, accompanied by a marked 133% increase in active MMP-2 values over that in the intact female group, was noted after treatment with compound 48/80 (P < or = 0.05), along with a significant reduction in collagen volume fraction below control (0.46 +/- 0.23 vs. 0.73 +/- 0.13%, P < or = 0.05). These findings indicate that estrogen's cardioprotective role can be partially mediated by its effects on cardiac mast cells, MMPs, and the extracellular matrix.
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PMID:Modulation of cardiac mast cell-mediated extracellular matrix degradation by estrogen. 1572 8

Radiation-induced heart disease (RIHD), characterized by accelerated atherosclerosis and adverse tissue remodeling, is a serious sequelae after radiotherapy of thoracic and chest wall tumors. Adverse cardiac remodeling in RIHD and other cardiac disorders is frequently accompanied by mast cell hyperplasia, suggesting that mast cells may affect the development of cardiac fibrosis. This study used a mast cell-deficient rat model to define the role of mast cells in RIHD. Mast cell-deficient rats (Ws/Ws) and mast cell-competent littermate controls (+/+) were exposed to 18 Gy localized single-dose irradiation of the heart. Six months after irradiation, cardiac function was examined by echocardiography and Langendorff-perfused isolated heart preparation, whereas structural changes were assessed using quantitative histology and immunohistochemical analysis. Mast cell-deficient rats exhibited more severe postradiation changes than mast cell-competent littermates. Hence, mast cell-deficient rats exhibited a greater upward/leftward shift in the left ventricular (LV) diastolic pressure-volume relationship (P = 0.001), a greater reduction in in vivo LV diastolic area (from 0.50 +/- 0.024 cm in age-matched controls to 0.24 +/- 0.032 cm after irradiation; P = 0.006), and a greater increase in LV posterior wall thickness (from 0.13 +/- 0.003 cm in age-matched controls to 0.15 +/- 0.003 cm after irradiation; P = 0.04). Structural analysis revealed more pronounced postradiation accumulation of interstitial collagen III but less myocardial degeneration in hearts from mast cell-deficient rats. These data show that the absence of mast cells accelerates the development of functional changes in the irradiated heart, particularly diastolic dysfunction, and suggest that, in contrast to what has been the prevailing assumption, the role of mast cells in RIHD is predominantly protective.
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PMID:Influence of mast cells on structural and functional manifestations of radiation-induced heart disease. 1583 39

Mast cells are critical effectors of allergic disease, and are now implicated in immune responses observed in arthritis, multiple sclerosis, and heart disease. Because of their role in inflammation, understanding how mast cells develop is of clinical importance. In this study we determined the effects of IFN-gamma on mast cell survival. Using in vitro culture of bone marrow cells in IL-3 plus stem cell factor, we found that the addition of IFN-gamma induced apoptosis, as exhibited by the presence of subdiploid DNA and caspase activation. IFN-gamma-mediated apoptosis was Stat1-dependent, and was accompanied by loss of mitochondrial membrane potential. Apoptosis was reduced in cultures of bone marrow cells derived from p53- or Bax-deficient mice, as well as H2K-Bcl-2 transgenic mice. IFN-gamma hyperresponsiveness has been shown to result in inflammatory disease and death in mice lacking the regulatory protein suppressor of cytokine signaling (SOCS)-1. Bone marrow cells from SOCS-1 knockout (KO) mice failed to give rise to viable mast cells after culture in IL-3 plus stem cell factor, with profound apoptosis occurring as the cultures matured. However, bone marrow cells lacking both SOCS-1 and IFN-gamma survived normally. This in vitro defect in mast cell development was recapitulated in vivo. SOCS-1 KO mice demonstrated a 67% decrease in peritoneal mast cell numbers relative to wild-type mice, a deficiency that was reversed in SOCS-1/IFN-gamma KO mice. These data demonstrate the potent regulatory effects of IFN-gamma on mast cell survival and show that this cytokine can elicit mast cell death in vitro and in vivo.
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PMID:IFN-gamma induces apoptosis in developing mast cells. 1611 87

Mast cells are potent effectors of the inflammatory response, playing an important role in atopy, bacterial immunity, and animal models of arthritis, multiple sclerosis, and heart disease. Hence controlling mast cell numbers and responsiveness is essential for preventing inflammatory disease. We demonstrate that the cytokine transforming growth factor (TGF) beta1 is a potent inducer of mast cell apoptosis, a finding that was consistent in cultured mouse bone marrow-derived mast cells, peritoneal mast cells, and human mast cells. Cell death appeared to be caused by TGF-mediated repression of interleukin-3 (IL-3) receptor expression and function, leading to mitochondrial damage and activation of an apoptotic cascade acting via p53 and caspases. Although IL-3 receptor expression was reduced within 1 day of TGFbeta1 stimulation, apoptosis required at least 3 days to occur. This delay in onset is postulated to allow protective mast cell effector functions, protecting the host from infection while preventing the establishment of chronic inflammation. Our data support the theory that TGFbeta1 is an inhibitor of mast cell survival. The widespread expression of TGFbeta1 offers this cytokine as an ideal candidate for control of mast cell homeostasis.
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PMID:TGFbeta1 induces mast cell apoptosis. 1664 63

The mast cell (MC) inflammatory response is now linked not only to atopy, but also to arthritis, multiple sclerosis, heart disease, and resistance to bacterial infection. In the current study, we demonstrate that the signal transducer and activator of transcription 5 (Stat5) is rapidly activated by IgE cross-linkage, and that its expression is critical to the MC response. Stat5-deficient (Stat5KO) MC demonstrated a significant decrease in IgE-mediated degranulation, leukotriene B4 production, cytokine secretion, and survival signals. The defect in cytokine production may be caused by decreased cytokine mRNA stability. Stat5KO MC-induced cytokine mRNAs normally following IgE cross-linkage, but these mRNAs were not sustained over time and were degraded at twice the rate observed in WT cells. Interestingly, the RNA destabilizing protein tristetraprolin was induced following IgE cross-linkage in Stat5KO but not wild-type cells. Moreover, reducing tristetraprolin expression via short hairpin RNA transfection significantly increased IL-13 production in Stat5KO MC. Our work demonstrates that Stat5 is a critical factor in IgE-induced MC activation, acting in part via posttranscriptional control of cytokine mRNA stability. These data have a direct impact on MC-associated inflammatory and autoimmune diseases.
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PMID:Stat5 expression is required for IgE-mediated mast cell function. 1692 Sep 84

Mast cells are believed to be involved in myocardial tissue remodelling under pathophysiological conditions. We examined the effects of autoantibodies against G-protein-coupled receptors in sera of patients with heart diseases on myocardial mast cells in the cultured neonatal Sprague-Dawley rat heart cells. Cells collected at day 3 and 10 of the culture were preincubated with autoantibodies against alpha1-adrenoceptor and angiotensin II AT1-receptor, agonist phenylephrine and angiotensin II, and control IgG. The pretreated cultured cells were stained for selected mast cell markers tryptase, chymase and TNF-alpha. The cultured cells were also processed for observation with electron microscopy. The autoantibodies-treatment of the 3-day cultured cells caused both increased intensity of immunofluorescence (p < 0.05) and their enlarged diameters of the mast cells when compared to age-matched ones. In contrast, the fluorescence of preincubated 10-day-old mast cells was decreased compared with controls (p < 0.01). In control samples, the fluorescence of 10-day-old mast cells was significantly higher than that of 3-day-old ones (p < 0.001). Results of electron microscopy examination demonstrated there was an increased granulation of treated 3-day-old mast cells, while a degranulation of mast cells at day 10 of application. The results suggest the modulation effect of the autoantibodies against G-protein-coupled receptors on mast cells, indicating a potential functional link between the autoantibodies against G-protein-coupled receptors and the mast cells in progression of heart disease.
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PMID:Autoantibodies against G-protein-coupled receptors modulate heart mast cells. 1748 7

Radiation-induced heart disease is a severe side effect of thoracic radiotherapy. Studies suggest that mast cells play a protective role in radiation-induced heart disease and that the endothelin (ET) system mediates protective effects of mast cells in other disorders. This study examined whether mast cells modulate the cardiac ET system and examined the effects of ET receptor inhibition in a rat model of radiation-induced heart disease. Mast cell-deficient (Ws/Ws), mast cell-competent (+/+) and Sprague-Dawley rats received 18 Gy irradiation to the heart. Left ventricular mRNA of ET1 and its receptors (ETA and ETB) was measured in Ws/Ws and +/+ rats at 1 week and 3 months. Sprague-Dawley rats were treated with the ETA/ETB antagonist bosentan, and at 6 months cardiac changes were assessed using the Langendorff perfused rat heart preparation, immunohistochemistry and real-time PCR. Ws/Ws and +/+ rat hearts did not differ in baseline mRNA. In contrast, +/+ rats hearts exhibited up-regulation of ET1 after irradiation, whereas Ws/Ws rats hearts did not, suggesting the possibility of interactions between mast cells and the cardiac ET system. Bosentan induced reductions in left ventricular systolic pressure, developed pressure and +dP/dtmax but did not affect fibrosis. Because of the known opposing effects of ETA and ETB, studies with selective antagonists may clarify the role of each receptor.
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PMID:Influence of endothelin 1 receptor inhibition on functional, structural and molecular changes in the rat heart after irradiation. 1876 54


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