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)

It has been previously demonstrated that iontophoresis of beta adrenergic agents will alter the size of immediate hypersensitivity skin tests. It was unclear whether this alteration was due to an effect on the dermal mast cell (inhibition of histamine release) or on the cutaneous vasculature (inhibition of capillary permeability). For this reason isoproterenol, propranolol, diphenhydramine as a positive control, and saline as a negative control were iontophoresed onto the forearm of 10 atopic and 10 nonatopic adult subjects. In order to bypass histamine release from mast cells the patients were then challenged directly with histamine by the "prick" technique. The size of the resultant wheals was noted. The data obtained allowed the following conclusions: (1) The atopic group responded to histamine with greater wheal size than the nonatopic group. (2) Iontophoresis of diphyenhydramine effectively reduced the magnitude of the histamine wheal in both groups. (3) Isoproterenol decreased the wheal size in both groups. (4) Propranolol increased the wheal size in only the nonatopic group. (5) The successful modulation of the histamine-induced wheal and flare indicated that these drugs, regardless of their effect on the dermal mast cell, exert a measurable effect on the target organ (vasculature).
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PMID:Effect of beta adrenergic stimulation and blockade on cutaneous reactivity to histamine. 0 84

IgE antibodies are usually thought to induce only immediate skin reactions. We have shown that the intradermal injection of a number of different allergens can produce a prolonged inflammatory reaction after the immediate wheal and flare in most sensitive subjects. This late inflammatory response occurs 6-12 h after challenge and is characterized by diffuse edema, erythema, pruritus, and heat. Both immediate and late responses can also be seen after passive sensitization of skin sites in nonatopic subjects. That IgE is involved in inducing the reaction was shown by the abolition of both immediate and late responses by passive transfer tests in the following experiments: (a) heating atopic serum at 56degreesC for 4 h, (b) removing IgE from the atopic serum by a solid phase anti-IgE immunoabsorbent, and (c) competitively inhibiting the binding of IgE antibodies to cells by an IgE myeloma protein. In addition, both responses were induced by affinity chromatography-purified IgE antibody, followed by antigenic challenge. Very similar lesions could also be induced by intradermal injection of Compound 48/80, thus suggesting a central role in the reaction for the mast cell or basophil. Histologically, the late phase is characterized by edema and a mixed cellular infiltration, predominantly lymphocytic but also containing eosinophils, neutrophils and basophils. Direct immunofluorescent staining did not show deposition of immunoglobulins or complement components, except IgM in 2 of 15 and C3 in 1 of 15 patients. This finding indicates that the late phase does not depend on the deposition of immune complexes. The results of the study suggest that IgE-allergen interaction on the surfaces of mast cells or on infiltrating basophils causes both immediate and late cutaneous responses.
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PMID:The late phase of the immediate wheal and flare skin reaction. Its dependence upon IgE antibodies. 78 99

The capacity of the beta 2-agonist terbutaline and the longer-acting beta 2-agonist formoterol to suppress the development of late phase skin reactions to anti-human IgE was evaluated in 17 healthy volunteers. Anti-IgE injected intradermally per se induced an early weal and flare reaction, followed by a progressively increasing induration, the LCR, with a duration of greater than or equal to 24 hr. The LCR was inhibited by 40% when the weal was infiltrated with formoterol 250 ng 30 min after challenge (n = 9, P less than 0.01). The same anti-LCR effect was achieved by compensating for the shorter duration of action of terbutaline with repeated drug infiltration in 12.5 micrograms doses of the weal produced by anti-IgE up to 3 1/2 hr after challenge (n = 8). The data support the hypothesis that beta 2-agonists, both short- and long-acting, inhibit IgE-dependent LCRs by preferentially interacting with inflammatory events after the initial mast cell degranulation.
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PMID:Inhibitory effects of formoterol and terbutaline on the development of late phase skin reactions. 134 58

Allergic cutaneous challenge causes mast cell and basophil mediator release which recruit inflammatory cells to the site of antigen administration. This secondary cell infiltration and mediator release is responsible for the changes seen during the late phase of allergic diseases. In this randomised, double-blind, cross-over, placebo controlled study, it was demonstrated that, at steady-state drug concentrations, chlorpheniramine reduced the wheal-and-flare reaction by about 50% compared to the 75% reduction, on average, by cetirizine and ketotifen. Cetirizine significantly reduced eosinophil vacuolisation at all observation periods, i.e. 2,6,10 and 24 h, and also inhibited basophil accumulation significantly at 10 h (75% reduction), while chlorpheniramine had a negligible effect on these variables. These changes would indicate that the late phase reaction was modified, especially as eosinophil vacuolisation is known to correlate with late phase intensity, T-lymphocyte infiltration and subsequent tissue damage. It further supports previous speculation that cetirizine inhibit late histamine release by acting on basophils. The extent of induration in the late phase reaction did not differ significantly among the three treatments. Cetirizine and ketotifen, noticeably although not significantly, reduced eosinophil and lymphocyte recruitment. As these two antihistamines differ structurally and in regard to receptor specificity, it is possible that they exert their actions on other, unspecified, receptors.
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PMID:Effect of cetirizine, ketotifen and chlorpheniramine on the dynamics of the cutaneous hypersensitivity reaction: a comparative study. 135 26

This study examined cutaneous mast cell behaviour in 14 patients with chronic urticaria but no dermographism and 11 healthy controls, by measuring cutaneous weal and flare reactions evoked in response to intradermal challenge injections of 0.1 ml isotonic saline, histamine (20 micrograms), codeine phosphate (10 micrograms) and compound 48/80 (10 micrograms). Five minutes after each injection, the area of the resulting weal and flare was calculated by computer-aided planimetry. The process was repeated at 15, 30 and 45 min following the injection. In patients, saline flares were significantly larger than those of the volunteers at 15, 30 and 45 min (p < 0.05). However, histamine and codeine flare areas were significantly smaller in the patients when compared to the controls at 15, 30 and 45 min (p < 0.05). Compound 48/80 produced smaller reactions in the patients without reaching statistical significance.
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PMID:Aberrant cutaneous weal and flare responses in chronic urticaria. 136 42

Heparin has been shown to act as a competitive inhibitor of inositol 1,4,5-triphosphate (InsP3) receptors in various cell types. Because InsP3 is one of the second messengers involved in stimulus-secretion coupling in mast cells, it is possible that heparin may inhibit mast cell-mediated reactions. Therefore, in allergic sheep, we tested this hypothesis in two mast cell-mediated reactions induced by immunologic and nonimmunologic stimuli: immediate cutaneous reaction (ICR) and acute bronchoconstrictor response (ABR). In 12 sheep allergic to Ascaris suum antigen, the surface area of the skin wheal was determined 20 min after intradermal injection (0.05 ml) of increasing concentrations of specific antigen, compound 48/80, and histamine, without and after pretreatment with heparin (100, 300, or 1,000 U/kg i.v.). Antigen, compound 48/80, and histamine produced concentration-dependent increases in ICR. Heparin "partially" inhibited the ICR to antigen and compound 48/80 in a dose-dependent manner without modifying the ICR to histamine. The heparin preservative benzyl alcohol was ineffective. In 11 additional sheep, specific lung resistance was measured before and after inhalation challenges with antigen, compound 48/80, and histamine without and with aerosol heparin pretreatment (1,000 U/kg). Heparin blocked the antigen- and compound 48/80-induced bronchoconstriction without modifying the airway effects of histamine. In isolated human uterine mast cells, heparin inhibited the anti-immunoglobulin E- but not the calcium ionophore- (A23187) induced histamine release. These data suggest that heparin inhibits the ICR and ABR induced by stimuli that produce immunologic and nonimmunologic mast cell degranulation without attenuating the effects of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunologic mast cell-mediated responses and histamine release are attenuated by heparin. 138 85

The flare and weal reactions to intradermal injections of histamine and the peptide substance P were measured in a group of patients with atopic dermatitis and compared to reactions in a non-atopic control group. There was no significant difference in the flare areas between the controls and atopics with either reagent. The weal volumes after injection of substance P and histamine were significantly larger in the atopic group. As substance P causes mast cell histamine release, the increased weal volumes produced by substance P in the atopics may be entirely due to the exaggerated atopic weal reaction to histamine.
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PMID:Cutaneous reactions to substance P and histamine in atopic dermatitis. 169 Oct 13

The immediate skin test due to interaction between allergen and mast cell bound IgE is one of the cornerstones in the clinical allergy workup. The release of histamine and other mediators from basophils and mast cells depends on the influx of Ca2+ into these cells when stimulated. The aim of this study was to evaluate the effect of common therapeutic doses of nifedipine (NFD), one of the calcium channel blockers, on the allergen skin tests. We prick tested 23 grass sensitive individuals with 7 different grass pollens at three times: at basal conditions (T0), 30 min. after having taken 20 mg of NFD s. l. (T1), and 17 of them after a week of receiving twice a day 20 mg of a NFD retard form (T2). The wheal surface obtained for each substance (allergen, histamine) at T0 was considered as basal value and compared with the one obtained at T1 and T2 for the same substance by the Wilcoxon's test. We found a significant increase in the wheal surfaces, both with allergen and histamine, at T1 and T2. In contrast to what could be expected, common therapeutic doses of NFD produce a discrete but statistically significant increase of the PT. Factors such as arteriolar vasodilation could be implicated. The increase of the allergen prick test and the increase of the histamine prick test both at T1 and T2 were not statistically different. Therefore, we do not think it necessary to stop NFD before allergen skin testing.
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PMID:Effect of nifedipine on skin prick tests. 169 76

Histamine H1-antagonists inhibit the weal-and-flare responses to the intradermal injection of platelet activating factor (PAF) in humans, and PAF response is reduced in histamine-depleted skin sites. This indicates that mast cell histamine release is likely to be the mechanism of this response. We have therefore studied the interaction of PAF with cutaneous mast cells by observing whether it releases histamine directly from human dispersed foreskin mast cells, potentiates the activity of known mast cell stimulants or liberates histamine releasing factors (HRFs) from human platelets and leucocytes to release mast cell histamine by an indirect mechanism. At a concentration of 100 microM both PAF C18 and PAF C16 caused near maximal release (83.5 +/- 4.3% and 88.2 +/- 4.5% respectively) of the total histamine content of the cell. This release was not inhibited in the absence of extracellular Ca2+, by the lack of metabolic energy or in the presence of the PAF antagonists WEB 2086 (100 nM-3 microM) or BN 52021 (100 nM-10 microM). These results indicate a cytotoxic mechanism of histamine release by PAF 100 microM. PAF (10 nM-1 microM) failed to potentiate the mast cell-stimulating activity of anti-IgE, calcium ionophore A23187 or substance P and it did not induce the release of HRFs for skin mast cells when incubated with platelets and leucocytes in concentrations up to 1 microM.
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PMID:Platelet activating factor does not release histamine from human dispersed cutaneous mast cells. 169 68

1. To test the hypothesis that the in vivo inhibition of angiotensin converting enzyme in a patient who presents atopy, results in a significant increase in cutaneous bradykinin and prostaglandin production, the effect of enalapril on the cutaneous hypersensitivity reaction was examined in 10 atopic volunteers. 2. A crossover study design was used and volunteers were randomly allocated to treatment with either enalapril (10 mg) alone, or in combination with indomethacin (75 mg), with and without ketotifen (1 mg). Drugs were administered twice daily for 2 days. 3. Allergen (Southern Grass Mix) was administered intradermally 2 h after last drug dosage and the surface areas of the immediate wheal-and-flare-reactions were measured 15 min later. The late phase of the cutaneous response was evaluated 6 h later by determining skinfold thickness and surface area. 4. Enalapril alone had no effect on any of the parameters measured. 5. The cutaneous hypersensitivity reaction was significantly reduced with regard to both immediate and late cutaneous responses when the indomethacin and ketotifen combination was added to enalapril therapy. 6. When only indomethacin was added to enalapril pretreatment the flare reaction was significantly reduced, but whealing was unaffected. 7. This study presents further evidence that mast cell mediators other than prostaglandins are involved in the cutaneous hypersensitivity reaction. Furthermore, that endogenous bradykinin production after enalapril pretreatment either never reaches the supraphysiological concentrations used in previous experiments, or that bradykinin is rapidly and effectively broken down to inactive peptides by other carboxypeptidase enzymes.
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PMID:Effect of enalapril on allergen-induced cutaneous hypersensitivity reaction. 176 63


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