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)

Due to increases in life expectancy, women are living 30 years or more beyond menopause. This has led to an increasing interest in the association between postmenopausal estrogen deficiency and degenerative diseases associated with aging such as cardiovascular disease, osteoporosis and dementia. Women are two times more likely to develop late-onset Alzheimer's disease (AD) than age-matched men. A large number of observational reports and a few randomized clinical trials have indicated that estrogen replacement therapy (ERT) may retard the development and severity of dementia in postmenopausal women. The mechanism underlying the protective action of estrogen in AD is under active investigation. A chronic inflammatory reaction mediated by abnormal deposition of proteins such as amyloid-beta (A beta) is central to the pathology of AD. We investigated the effect of low doses of conjugated estrogen (Premarin) in an animal model of A beta-induced vascular disruption and inflammatory reaction. This rodent model allows live videomicroscopic recording and electron microscopic analysis of peripheral vascular disruption and inflammatory reaction triggered by A beta. Estrogen prevented vascular deposition of A beta, endothelial and vessel wall disruption with plasma leakage, platelet and mast cell activation, and characteristic features of an inflammatory reaction: adhesion and transmigration of leukocytes. The beneficial effect was lost when estrogen treatment was discontinued. Estrogen also protected the cerebral blood vessels from endothelial dysfunction induced by A beta. This novel protective effect of estrogen against A beta cytotoxicity in peripheral and cerebral vasculature may contribute to the therapeutic efficacy of estrogen in AD and coronary vascular disease.
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PMID:Estrogen protects peripheral and cerebral blood vessels from toxicity of Alzheimer peptide amyloid-beta and inflammatory reaction. 1068 97

Women are two to three times more likely to develop late-onset Alzheimer's disease (AD) than age-matched men. A large number of observational reports and a few randomized clinical trials have indicated that estrogen replacement therapy (ERT) may retard the development and severity of dementia in postmenopausal women. A chronic inflammatory reaction mediated by abnormal deposition of proteins such as amyloid-beta (A beta) is central to the pathology of AD. We investigated the effect of low doses of conjugated estrogen (Premarin) in an animal model of A beta-induced vascular disruption and inflammatory reaction. Estrogen prevented vascular deposition of A beta, endothelial and vessel wall disruption with plasma leakage, platelet and mast cell activation, and characteristic features of an inflammatory reaction: adhesion and transmigration of leukocytes. The beneficial effect was lost when estrogen treatment was discontinued. This novel protective effect of estrogen against A beta-induced vascular dysfunction may contribute to the therapeutic efficacy of estrogen in AD and coronary vascular disease.
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PMID:Vascular actions of estrogen and Alzheimer's disease. 1081 45

This review provides a survey on mast cell heterogeneity, with aspects differing in humans and rodents or which are subject of conflicting evidence being discussed in greater detail. Mast cell subsets have been first defined in rats by their fixation and dye-binding properties, and detailed studies in humans and pigs reveal very similar observations. The dye-binding properties of rat mast cell subsets are causally related to the absence or presence of heparin in their granules. In humans, this relation has not been shown. Rodent mast cell subsets store different chymase-isoforms. In contrast, just a single chymase has been defined in humans, and mast cells are classified by the presence or relative absence of this chymase. Different investigators find quite different proportions of chymase-positive to chymase-negative mast cells. Tryptase(s) are found in most or every human mast cell, but in rodents, they have hitherto been essentially localised to mast cells in connective tissues. Human mast cell subsets may also be defined by their expression of receptors such as C5aR and possibly the beta-chemokine receptor CCR3; the CCR3 expression seems to be related to the human mast cell chymase expression. Ultrastructural studies are helpful to distinguish human mast cell subsets, and allow to distinguish between chronic and acute activation. The phenotypical characteristics may change in association with inflammation or other disease processes. Studies in humans and pigs show changed dye-binding and fixation properties of the granules. Experimental rodent infection models reveal similar changes of chymase isoform expression. Human lung mast cells have been reported to strongly upregulate their chymase content in pulmonary vascular disease. This line of evidence can explain some inconsistent information on mast cell heterogeneity and may help to understand the physiological role of mast cells.
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PMID:Mast cell granule composition and tissue location--a close correlation. 1096 36

Coagulation times and protamine titration values for heparin are apt to be lower than average in patients with allergic disease, particularly asthma. Severe asthma is commonly treated with gluco-corticoids or ACTH. Prolonged high dosage of gluco-corticoids, either endogenous or exogenous, depresses mast cell function and heparin production. Thrombo-embolic phenomena occur frequently in severe cases of asthma so treated, particularly if predisposing vascular disease is present. Heparin can be used to treat and prevent these complications. Adjuvant antiasthmatic effects under these conditions are noted in addition to the desired anticoagulation.
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PMID:Thrombo-embolic phenomena in severe asthma. Use of heparin for prevention and treatment in patients receiving ACTH or gluco-steroids. 1395 39

Chymase is a chymotrypsin-like serine protease secreted from mast cells. Mammalian chymases are classified into two subgroups (alpha and beta) according to structure and substrate specificity; human chymase is an alpha-chymase. An important action of chymase is the ACE-independent conversion of Ang I to Ang II, but chymase also degrades the extracellular matrix, activates TGF-beta1 and IL-1beta, forms 31-amino acid endothelins and is involved in lipid metabolism. Under physiological conditions, the role of chymase in blood vessels is uncertain. In pathological situations, however, chymase may be important. In animal models of hypertension and atherosclerosis, chymase may be involved in lipid deposition and intimal and smooth muscle hyperplasia, at least in some vessels. In addition, chymase has pro-angiogenic properties. In human diseased blood vessels (e.g. atherosclerotic and aneurysmal aorta; remodeled pulmonary blood vessels), there are increases in chymase-containing mast cells and/or in chymase-dependent conversion of Ang I to Ang II. These findings have raised the possibility that inhibition of chymase may have a role in the therapy of vascular disease. The effects of chymase can theoretically be attenuated either by reducing availability of the enzyme, with a mast cell stabiliser, or alternatively with specific chymase inhibitors. The mast cell stabiliser, tranilast, was shown to be beneficial in animal models of atherosclerosis, where a prevention protocol was used, but was not effective in clinical trials where it was administered after angioplasty. Chymase inhibitors could have the advantage of being effective even if used after injury. Several orally active inhibitors, including SUN-C8257, BCEAB, NK3201 and TEI-E548, are now available. These have yet to be tested in humans, but promising results have been obtained in animal models of atherosclerosis and angiogenesis. It is concluded that orally active inhibitors of chymase may have a place in the treatment of vascular diseases where injury-induced mast cell degranulation contributes to the pathology.
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PMID:Vascular chymase: pathophysiological role and therapeutic potential of inhibition. 1498 62

Many previous epidemiological studies have revealed that green tea or green tea catechins contributed to the preveintion of lifestyle-related diseases. Several cohort studies on the relationship between green tea consumption and cardiovascular disease (CVD) risk/type 2 diabetes mellitus risk have been conducted. The results showed that green tea consumption (5 or more cups/day) was inversely associated with mortality from CVD and all causes. Within CVD mortality, the strongest inverse association was observed for stroke mortality. Furthermore, consumption of green tea, coffee, and total caffeine was associated with a reduced risk for type 2 diabetes. On the other hand, the analysis of randomized clinical trial (RCT) studies showed that the administration of green tea beverages or extracts resulted in significant reductions in serum total cholesterol and LDL-cholesterol concentrations, but had no apparent effect on HDL-cholesterol. Green tea reduced fasting blood glucose levels in a small intervention trial, although no improvements in HbA1c levels were seen. Continuous intake of green tea containing catechins and caffeine (5 or more cups per day) may be beneficial for body weight management, vascular disease risk reduction via LDL-cholesterol improvement, and type 2 diabetes risk reduction through the lowering of fasting blood glucose levels. Epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3"Me) isolated from cv. "Benifuuki" green tea has been shown to strongly inhibit mast cell activation and histamine release after FcepsilonRI cross-linking through the suppression of tyrosine phosphorylation (Lyn) of cellular protein kinase, and the suppression of myosin light chain phosphorylation and high-affinity IgE receptor expression via the binding to 67 kDa laminin receptors. A double-blind clinical study on subjects with Japanese cedar pollinosis was carried out. At the eleventh week after starting intake, which was coincident with the most severe period of cedar pollen-scattering, symptoms such as nose blowing and eye itching were significantly relieved in the Benifuuki group compared with the placebo group. Six weeks of intake of Benifuuki green tea containing O-methylated catechins was useful for reducing some of the symptoms derived from Japanese cedar pollinosis, and did not affect any of the normal immune responses in the subjects with Japanese cedar pollinosis. Based on an investigation into the effects of the cultivars, tea seasons of crops and manufacturing methods, it was concluded that green or semi-fermented tea made from fully-matured Benifuuki in the second crop season should be consumed.
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PMID:Human clinical studies of tea polyphenols in allergy or life style-related diseases. 2344 49

Mast cells are important cells of the immune system. Although traditionally considered as key players in allergic and hypersensitivity reactions, emerging evidence suggests that mast cells have many complex roles in vascular disease. These include regulation of vasodilation, angiogenesis, activation of matrix metalloproteinases, apoptosis of smooth muscle cells, and activation of the renin angiotensin system. Mast cells are also known to play an immunomodulatory role via modulation of regulatory T-cell (Treg), macrophage and endothelial cell functions. This dual role of the mast cells is evident in myeloperoxidase anti-neutrophil cytoplasmic antibodies-mouse model of glomerulonephritis in which mast cell deficiency worsens glomerulonephritis, whereas inhibition of mast cell degranulation is effective in abrogating the development of glomerulonephritis. Our previous work demonstrated that mast cell degranulation inhibits lipopolysaccharide-induced interleukin 6 (IL-6) production in mice. This effect was not seen in histamine-1-receptor knockout (H1R-/-) mice suggesting a role for histamine in IL-6 homeostasis. In addition, mast cell degranulation-mediated decrease in IL-6 production was associated with an upregulation of suppressor of cytokine signaling-1 protein in the aorta. We propose that mast cells regulate large artery inflammation through T-cells, shifting a primarily Th1 and Th17 toward a Th2 response and leading to enhanced IL-10 production, activation Treg cells, and the inhibition of macrophage functions.
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PMID:Protective Role of Mast Cells in Primary Systemic Vasculitis: A Perspective. 2887 69

Mast cells are typically linked to immediate hypersensitivity and anaphylaxis. This review looks beyond this narrow role, focusing on how these cells have evolved and diversified via natural selection promoting serine protease gene duplication, augmenting their innate host defense function against helminths and snake envenomation. Plasticity of mast cell genes has come at a price. Somatic activating mutations in the mast cell growth factor KIT gene cause cutaneous mastocytosis in young children and systemic mastocytosis with a more guarded prognosis in adults who may also harbor other gene mutations with oncogenic potential as they age. Allelic TPSAB1 gene duplication associated with higher basal mast cell tryptase is possibly one of the commonest autosomal dominantly inherited multi-system diseases affecting the skin, gastrointestinal tract, circulation and musculoskeletal system. Mast cells are also establishing a new-found importance in severe asthma, and in remodeling of blood vessels in cancer and atherosclerotic vascular disease. Furthermore, recent evidence suggests that mast cells sense changes in oxygen tension, particularly in neonates, and that subsequent degranulation may contribute to common lung, eye, and brain diseases of prematurity classically associated with hypoxic insults. One hundred and forty years since Paul Ehrlich's initial description of "mastzellen," this review collates and highlights the complex and diverse roles that mast cells play in health and disease.
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PMID:Mast cell disorders: From infancy to maturity. 3039 Mar 14