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 events which lead to airway narrowing in bronchial asthma are complex. There is little doubt that mast cell-derived pharmacological agents are involved, at least in part, in the initiation of the asthmatic response. However, the inflammatory response which follows mast cell activation might have more relevance to the daily pattern of asthma than the direct effects of mediators on bronchial tissue. Although the IgE mediated release of mediators from sensitized mast cells seems to play a role in pathogenesis in some individuals for some of the time, there is now increasing awareness that mast cells are also triggered by a number of non-immunological stimuli such as exercise/cold air, infection and agents which activate the complement system. Mast cell mediators are either pre-formed within granules or generated from membrane-bound phospholipids. The pre-formed mediators include histamine, various chemotactic peptides including ECF-A and the high molecular weight neutrophil chemotactic factor (NCF), proteases, glycosidases, and the heparin proteoglycan. The membrane-derived agents include the lipoxygenase products (e.g. LTB4 and the "SRS-A" leukotrienes-LTC4/D4/E4), prostaglandins and thromboxane in addition to the PAF-ace-tether (AGEPC). The mediators are diverse both in chemical composition and modes of actions. However, many of the pathological features of bronchial asthma can be explained on the basis of their recognised actions. These can be summarised as follows. Bronchial smooth muscle constriction (histamine, LTC4, LTD4, LTE4, PGF2 alfa, PGD2 and PAF); mucosal oedema (increased permeability--histamine, LTC4, LTD4 and PAF; vasodilation--PGD2, PGE2); mucous plugging (histamine, mono-HETEs and LTC4); inflammatory cell infiltrate (NCF, ECF-A peptides, HETEs, LTB4 and PAF); desquamation of epithelium (proteases, glycosidases, together with lysosomal enzymes, and basic proteins derived from neutrophils and eosinophils). It is likely that mild, easily reversible, episodic asthma is due largely to bronchial smooth muscle contraction whereas the late sustained response is more indicative of an inflammatory response, and dependent on the infiltration of neutrophils and eosinophils as the result of mediators which recruit and activate leucocytes. Much of the evidence for this is based on the demonstration that NCF concentrations in the serum are elevated during early and late phase, antigen- and exercise-induced asthma. Moderate to severe asthma is likely to be largely dependent on a subacute/chronic inflammation of the bronchi with eosinophils and mononuclear cells being prominent.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mediators of hypersensitivity and inflammatory cells in the pathogenesis of bronchial asthma. 641 59

Five individuals with idiopathic cold urticaria but not normal volunteers released platelet factor 4 (PF4) detected by radioimmunoassay into the circulation after cold challenge. In three patients, a biphasic rise in PF4 was noted with increases at 1 and 10 to 20 min after immersion, whereas in two others only the later rise was detected. Peak levels of PF4 were detected in all five patients 20 min after cold immersion, whereas peak levels of other mediators such as histamine and eosinophil and neutrophil chemotactic activity occurred earlier at 10, 3 to 10, and 5 to 10 min, respectively. The identification of PF4 in the circulation of patients with cold urticaria after cold challenge provides further evidence for the activation of platelets in mast cell-dependent disorders and suggests new potential mechanisms for the expression of cold urticaria.
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PMID:Release of platelet factor 4 into the blood after cold challenge of patients with cold urticaria. 647 Mar 62

A patient with symptomatic urticaria pigmentosa who responded to nifedipine therapy is reported. Relief from cold-induced urtication and flushing was obtained with 10 mg taken orally three times daily. Calcium influx is an early step in the degranulation of mast cells. We hypothesize that the beneficial effect of nifedipine was due to calcium-channel blockade causing elevation of the mast cell threshold for degranulation.
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PMID:Urticaria pigmentosa responsive to nifedipine. 649 Oct

Three subjects diagnosed as having idiopathic acquired cold urticaria were studied to assess the ability of orally administered tiaramide to inhibit the wheal induced following cold challenge with ice cubes placed in contact with the skin, and to establish the safety of multiple doses of 250 mg, q.i.d., for one week administered after a single oral dose of 500 mg. Two subjects completed the study. One subject was known to be unresponsive to antihistamines for allergy and the second was intolerant of antihistamines due to side effects. A third subject discontinued treatment due to an adverse reaction experienced while on the study medication. The skin of the forearm of each subject was exposed to cold stimuli for 1, 2, 3, 4, and 5 minutes by placing five ice cubes on the ventral surface at one minute intervals, and removing all simultaneously five minutes after contact with the first cube. The challenge sites were observed for ten minutes and the area of the wheal, intensity of edema and the time of contact necessary to induce the skin response were recorded. The results of this provocative test following the single and multiple dosage administration of tiaramide were compared to baseline skin responses. After one week of tiaramide treatment at 250 mg, q.i.d., both subjects who completed the study had a markedly attenuated skin response to cold challenge and no adverse effects. Our results suggest that absorbable compounds that can inhibit mast cell degranulation may be efficacious in cold urticaria and of particular value in treating patients who do not respond to standard therapy.
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PMID:Preliminary report on the effects of tiaramide on the ice cube test in patients with idiopathic cold urticaria. 663 14

The dynamic changes in skin mast cell (MC) numbers around incised wounds were studied, using experimental designs amenable to multiple analyses of variance. Sixty-four Wistar albino rats were shaved in the interscapular region, wounded or not wounded, and then killed 2 or 10 days later. During this period, the rats were exposed continually to a cold (2 degrees C) or control (20 degrees C) climate and treated daily over the shaved region with either tap water or a weak sulphuric acid (pH 3.5) solution. The MCs within five adjacent fields of the wound or the control reference and within the superficial and deep halves of the skin were counted (at x 400). The greatest decrease in MC numbers occurred within about 700 microns of the wound. Whereas the paucity of MCs within the wound region was evident at 2 days, near-normal levels were achieved by day 10. Cold exposure produced little effect, but MCs responded differently to the water and acid treatments as a function of distance and skin depth.
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PMID:Mast cell numbers in incisional wounds in rat skin as a function of distance, time and treatment. 682 75

Mast cells in skin are distributed around dermal and subcutaneous blood vessels. Activation of tissue mast cells produces secretion and/or generation and secretion of a variety of biologically active molecules. Mast-cell-dependent mediators may be classified as smooth-muscle-contracting and vasoactive activities, chemotactic factors, enzymes, and proteoglycans. These mediators alter the microenvironment to produce a biphasic response. The initial or humoral phase of the response is mediated by materials that alter vascular permeability; peripheral blood leukocytes attracted by chemotactic factors establish the cellular phase. Failure to limit the humoral phase creates a pharmacologic state that may be recognized in skin as urticaria/angioedema. The inability to control the cellular phase permits progression to a local inflammatory state with subacute and chronic tissue injury recognized in skin, for example, as necrotizing vasculitis. As an example of the former, certain forms of physical urticaria have provided experimental models in humans to allow observation of the clinical manifestations, study of tissue alterations by histologic analysis, measurement of mediators released into the circulation, and assessment of motility of peripheral blood leukocytes. An example of the role of the mast cell in the production of subacute and chronic inflammatory cutaneous disease is suggested by studies in a patient in whom exposure to the physical stimuli of cold and trauma was followed by initial mast cell degranulation, subsequent tissue deposition of circulating immune complexes, and the development of a necrotizing vasculitis.
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PMID:Mast cells in cutaneous inflammatory disorders. 685 53

Urticaria and angioedema may occur in skin and mucus membranes when mast cells are activated by various physical stimuli, including trauma, pressure, vibration, light, cold, heat, and (in rare cases) water. Experimental challenge of patients with cold-induced and cholinergic urticaria/angioedema in particular provides an in vivo model of mast cell activation in humans. This model synthesizes observations of the evolution of clinical manifestations, histologic analysis of tissue alterations, measurement of mediators released into the circulation, and assessment of leukocyte motility. The model in turn allows a characterization of mediators that exist preformed in mast cell granules or that are generated through interactions with other cell types. Release of these mediators produces a variety of biologic effects, including elaboration of certain enzymes and alterations in venular permeability, smooth muscle contraction, leukocyte motility, and the release of substances from other cell types.
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PMID:Physical urticaria/angioedema: an experimental model of mast cell activation in humans. 700 77

The eosinophilic activity appearing in the venous effluent of the cold-induced angioedematous extremity of patients with cold urticaria has been resolved into three fractions by gel filtration and Dowex-1 chromatography. The low molecular weight activity, 300-700 mw, is highly acidic while the activity of 1000-3000 mw is composed of highly acidic and less acidic moieties. Each of the three activities has a different retention time on high pressure liquid chromatography, indicating that they represent distinct fractions which differ in size, charge, and hydrophobicity. Each fraction requires a gradient to attract eosinophils in a dose-response fashion and each deactivates eosinophils at subchemotactic concentrations. The more acidic 1000-3000 mw fractions also attract human monocytes in a chemotactic gradient at concentrations identical to those which attract human eosinophils. These three classes of eosinophil chemotactic activities and the activity for monocytes appear and disappear from the venous effluent with essentially the same time course as a distinct neutrophil chemotactic factor and histamine with cold induction of angioedema in patients with cold urticaria. The elaboration of these diverse chemoattractants in experimentally induced physical allergy provides potential pathways for mast cell-mediated infiltrative reactions.
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PMID:The functional and physicochemical characterization of three eosinophilotactic activities released into the circulation by cold challenge of patients with cold urticaria. 708 32

Rabbit mesenteric artery strips exposed to 10(-3) M dithiothreitol (DTT) were contracted with a series of concentrations of histamine and 2-pyridylethylamine (PEA). DTT exposure increased the sensitivity to histamine 100-fold but increased the sensitivity to PEA only 4-fold. DTT did not reduce dimaprit-induced relaxations, but reduced histamine-induced relaxations. Following a high concentration of histamine (10(-3) M), DTT itself produced a sustained, slowly developing contraction (29 +/- 6.8% of the maximal contraction) relaxed by 7 X 10(-6) M mepyramine but not by 10(-6) M phentolamine. Metiamide (3 x 10(-5) M) potentiated DTT-induced contractions (29 +/- 6.8 before, 57 +/- 7.5% after metiamide, as a percent of maximal contraction). Changing the bathing fluid and repeating DTT exposure slowly relaxed previously contracted strips. DTT did not prevent the increase in sensitivity of relaxant histamine receptors on exposure to cold. We conclude that DTT, in addition to potentiating histamine H1-receptor responses, releases histamine presumably from non-mast cell pools when they are loaded with a high concentration of exogenous histamine.
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PMID:Effects of dithiothreitol on the isolated rabbit mesenteric artery. 718 Jul 33

We described the sixteenth reported case of local heat urticaria, in a 59-yr-old woman with erythema and angioedema upon contact with hot water or outdoor heat exposure. Immersing her hand in 39 degrees to 40 degrees C heated water resulted in an erythematous, angioedematous response sharply demarcated by the line of immersion and was associated with immediate increases in histamine concentration (18 to 135 ng/ml) and high molecular weight neutrophil chemotactic activity (two to five times prechallenge levels) in venous blood draining the challenge site. We suggest that the local heat urticarial response in this woman was a form of physical urticaria associated with release of mast cell-derived mediators, akin to cold and cholinergic urticaria.
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PMID:Mediator release in local heat urticaria. 728 47


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