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)

Urticaria, a cutaneous reaction pattern, varies clinically and histopathologically. The origin of acute urticaria can be detected in some cases; in patients with chronic urticaria, however, the cause is rarely identified. Thus, most patients with chronic urticaria are considered to have idiopathic disease. The dermal mast cell and its mediators may play a central role in chronic idiopathic urticaria. Other inflammatory cells, including lymphocytes and polymorphonuclear cells, have also been implicated. Treatment is based on identification of the inflammatory cells within skin lesions and blockage of the effects of histamine in the skin. Urticaria in which a lymphocyte-predominant infiltrate is seen often responds to one or more H1 antihistamines. Recently, a new generation of nonsedating or mildly sedating H1 antihistamines has proved useful in the management of these cases. Antihistamine use alone may be unsuccessful in urticaria in which polymorphonuclear neutrophils predominate; frequently, the addition of agents that alter polymorphonuclear neutrophil function, such as colchicine or dapsone, is required. During the introduction of antihistamine and anti-polymorphonuclear neutrophil therapy, a simultaneous brief course of systemic corticosteroid therapy may be necessary, but the extended use of systemic corticosteroids should be avoided because of significant adverse effects. As the pathophysiologic mechanisms responsible for chronic urticaria are better defined, more effective therapeutic agents should become available.
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PMID:Chronic urticaria: pathophysiology and treatment approaches. 897 44

Autoantibodies recognizing critical effector molecules of type I allergic reactions have been identified. Anti-IgE autoantibodies occur at high frequencies not only in atopic diseases but also in healthy individuals and, depending on their epitope specificities, may promote or prevent the elicitation of allergic symptoms. In contrast, anti-Fc epsilon RI autoantibodies with basophil/mast cell activating properties were selectively found in patients with chronic urticaria, a condition characterized by the continuous degranulation of mast cells. Thus, humoral anti-Fc epsilon RI autoreactivity defines a distinctive subset of chronic urticaria and may well be the causative and pathogenetic principle in this disease.
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PMID:Anti-IgE and anti-Fc epsilon RI autoantibodies in clinical allergy. 899 56

The underlying pathophysiology of chronic urticaria is mast cell activation, with release of histamine and other mast cell mediators. A weal producing factor has been identified in the serum of 60% of patients with chronic idiopathic urticaria. In half of these patients there is evidence for functional autoantibodies against the high affinity IgE receptor or IgE, or both. These autoantibodies release histamine from basophils and mast cells. It is therefore likely that there is an autoimmune basis for up to 30% of patients with idiopathic urticaria. In the other half of patients whose serum causes weals, the factor releases histamine from mast cells only and is as yet unidentified. So far no clinical difference has been associated with presence/absence or type of weal producing factor. Exacerbating factors in chronic urticaria such as aspirin, food additives, febrile illness and psychological stress should be identified and avoided. Treatment is symptomatic with the low sedation antihistamines. In the most severe cases not responding to conventional therapy and which may have the weal producing factor, treatments with non specific immune therapy such as cyclosporin, and intravenous gammaglobulin and also plasmapheresis have been promising.
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PMID:The pathogenesis of urticaria. 909 81

Treatment of chronic urticaria presents a challenge to both practitioner and patient. Traditional H1 antagonists with good efficacy but substantial side effects are being supplanted in many cases by nonsedating H1. Combinations of H1 and H2 antagonists offer improved results for selected patients. Second-line therapies include a wide range of drugs such as doxepin, dapsone, attenuated androgens, calcium antagonists, antimalarials, gold and methotrexate. The most effective and regularly used second-line agents are corticosteroids. These are best limited to short term crisis management, except in severe recalcitrant cases, and in patients with pressure urticaria or urticarial vasculitis. Further development and investigation of mast cell stabilisers and inhibitors of urticaria mediators other than histamine hold promise. A better understanding of the underlying pathogenesis remains the greatest hope of formulating rational and effective therapy.
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PMID:Pharmacologic therapy for urticaria. 911 75

Until relatively recently, the pathophysiologic significance of the recognized associations between autoimmunity and swelling was largely unknown. It has now become clear that autoimmunity can play a critical role in the pathogenesis of chronic urticaria and acquired C1-INH deficiency with angioedema. Chronic urticaria has been associated with antithyroid autoantibodies, anti-IgE autoantibodies, and anti-Fc epsilon RI autoantibodies. The latter two autoantibodies are particularly interesting in that they have been shown to be capable of directly causing mast cell degranulation. It appears likely, therefore, that most cases of chronic urticaria will ultimately be considered an autoimmune disease rather than an allergic disease. The link between autoimmunity and the development of acquired C1-INH deficiency is also of interest. Recent studies suggest that the majority of acquired C1-INH deficiency patients have anti-C1-INH autoantibodies that appear to be responsible for the development of the C1-INH deficiency. In addition, both chronic urticaria and C1-INH deficiency can be associated with other autoimmune diseases, although the importance of these associations remains to be determined. Recognition of the role of autoantibodies in the pathogenesis of chronic urticaria and acquired C1-INH deficiency has altered the range of diagnostic and therapeutic approaches that need to be considered in approaching patients with chronic urticaria or acquired C1-INH deficiency. Future progress in understanding the genesis of these diseases may help elucidate the mechanism of autoantibody generation.
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PMID:Urticaria, angioedema, and autoimmunity. 931 73

A patient with chronic urticaria and angioedema developed endoscopically confirmed interstitial cystitis. Bladder biopsy revealed bladder mastocytosis with > 60 mast cells/mm2 (normal < 10) in the detrusor and submucosa. Most of the mast cells were activated and degranulated. The occurrence of IC in a patient with urticaria and angioedema, diseases both associated with mast cell pathophysiology, supports the role of mast cells in interstitial cystitis.
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PMID:Interstitial cystitis and bladder mastocytosis in a woman with chronic urticaria. 940 15

Assays based on reporter gene technology represent today an important tool in the pharmaceutical industry for discovering novel compound classes interfering with the activation and signaling of target cells after stimulation. Here we describe a reporter gene assay targeting mast cell activation of IgE plus antigen, established in an attempt to identify substances preventing type I allergy (allergic rhinitis, allergic conjunctivitis, allergic asthma, and acute and chronic urticaria). The assay is based on a murine mast cell line designated CPII, stimulation by IgE plus antigen, and a reporter gene construct with the TNF alpha promoter linked to luciferase as a read-out system. Via screening about 50,000 substances, compound 2 was found to inhibit the reporter gene induction in the submicromolar range in this assay. Analogues of compound 2 of the 2,3,4-trihydropyrimidino[2,1-a]isoquinoline type were synthesized starting from 2-alkyl-substituted benzonitriles via aminolysis with 1,3-diaminopropane, dimetalation of 2-substituted 2-phenyl-1,4,5,6-tetrahydropyrimidines with n- and sec-butylithium, reaction with carboxylic acid methyl esters, and finally acidic dehydration. From about 50 derivatives, compound 41 was selected as a lead structure with an IC50 of 0.2 microM and a TC50 of 2.7 microM. In a first profiling in secondary assays, it effectively interfered with the production of mediators such as TNF alpha, IL-4, IL-6, IL-13, and leukotriene synthesis as measured by the corresponding ELISAs. In addition, a passive cutaneous anaphylaxis in mice (a typical type I reaction) is inhibited to more than 90% by compound 41, when administered intradermally 90 min before challenge.
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PMID:Inhibition of Fc epsilon RI-mediated activation of mast cells by 2,3,4-trihydropyrimidino[2,1-a]isoquinolines. 954 5

Neutrophilic urticaria (NU) is a histologically defined entity, but its clinical and pathogenetic aspects are poorly understood. We investigated 22 NU patients whom we identified by examining 118 biopsies of weals. The patients comprised 11 of 20 with acute urticaria, nine of 49 with chronic urticaria, one of 10 with cold urticaria and one of 10 controls undergoing prick tests. Clinically, NU patients had a shorter mean duration of disease than other urticaria patients and significantly increased erythrocyte sedimentation rate and leucocytosis. Histologically, not only neutrophil counts, but to a lesser extent also eosinophil counts and mononuclear cell infiltrates were significantly increased in lesional skin of NU, and there was more marked vasodilatation and endothelial swelling. On immunohistochemistry, increased tumour necrosis factor alpha and interleukin (IL)-3 expression was noted, compared with other urticarias, whereas IL-8 expression was only minor. These data characterize NU as an acute phase urticarial reaction associated with an intense inflammatory infiltrate and marked upregulation of some mast cell-derived cytokines.
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PMID:Neutrophilic urticaria: clinical features, histological changes and possible mechanisms. 960 69

This article is a review of the role of mast cells and other inflammatory cells in pathogenesis of chronic urticaria. The role of histamine in pathophysiology of chronic urticaria has been established but interaction between IgE-bound mast cells and allergen is unlikely to be the mechanism by which histamine release occurs. The authors present some factors trigger mast cell degranulation and mediator release as histamine releasing factor (HRF) generating by lymphocytes and IgE autoantibodies against mast cell and basophil IgE receptors.
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PMID:[Pathogenesis of chronic urticaria]. 1076 57

Although the etiology of urticaria is mostly unclear, there are a number of recent new insights into the underlying pathomechanisms and causes. Dermal mast cell numbers and endothelial cell adhesion molecule and cytokine expression are also increased in uninvolved skin, while serum P-selectin levels are elevated, suggesting a systemic activation of the cutaneous inflammatory system in urticaria. In all adults, but not children with indolent mastocytosis, we found activating point mutations of c-kit, the mast cell growth factor receptor, in lesional cutaneous mast cells. In acute urticaria, IgE-dependent mechanisms are only rarely involved (0.9%), in contrast to generally held beliefs, whereas acute upper respiratory infections (39.3%) and drug intolerance (9.2%) are more frequent. In chronic urticaria, pseudoallergies to food (73%) and more rarely chronic inflammatory gastrointestinal diseases (11%) play a major role, with avoidance or elimination of the eliciting factors leading to long term remission. On the basis of recent findings, autoantibodies must be viewed mostly as secondary rather than causative in chronic urticaria.
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PMID:[Urticaria. New developments and perspectives]. 1087 66


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