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 expression of the receptor for the anaphylatoxin C5a on mast cells was studied with three monoclonal antibodies directed to the N-terminal domain of the C5a receptor. Human skin was investigated by immunohistology applied to sequential 2 micron sections of acrylate-embedded tissues. All anti-C5a receptor antibodies stained c-kit+ or tryptase+ cells which were metachromatic after toluidine blue staining in normal human skin. The binding of anti-C5a receptor antibodies was inhibitable by a peptide representing the first 31 amino acids of the C5a receptor. A similar expression of C5a receptors was found on mast cells in chronic psoriatic plaques. However, C5a receptors were not detectable on mast cells in weal and flare reactions or in lesional skin of uticaria pigmentosa. These findings suggest that (1) anti-C5a receptor antibodies directed to the N-terminal domain of the receptor are suitable tools for the identification of mast cells in acrylate-embedded sections of human skin, (2) mast cell activation in weal and flare reactions results in C5a receptor downregulation or receptor blockade and (3) mast cells in urticaria pigmentosa lack a typical marker of normal human skin mast cells.
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PMID:C5a receptors are detectable on mast cells in normal human skin and in psoriatic plaques but not in weal and flare reactions or in uticaria pigmentosa by immunohistochemistry. 904 41

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

1. Atopy is a genetically heterogeneous disorder, but there is now strong evidence that one important locus is on chromosome 11q13. Fc epsilon RI-beta at that location has been identified as a candidate gene and variants have been associated with atopy in population studies. 2. No information is available on the functional consequences of any of these variants, and defining this may prove difficult because of the complexity of the atopy phenotype and because Fc epsilon RI beta is expressed on a range of cells with different functions, including basophils, mast cells, eosinophils and antigen-presenting Langerhan's cells. 3. We have conducted a qualitative study of mast cell and basophil histamine release in nine atopic individuals with Ile-181-->Leu mutation of Fc epsilon RI beta, and ten unrelated similarly atopic individuals without Ile-181-->Leu mutation. There were non-significant trends for Ile-181-->Leu-positive atopic subjects to produce wheal responses at lower allergen challenge in skin prick tests, and to release more histamine from basophils following in vitro allergen challenge. 4. The data do not provide decisive evidence of functional differences between atopic subjects with Ile-181-->Leu and other atopic individuals; more discriminating functional experiments are required.
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PMID:Functional analysis of histamine release from basophils and mast cells in subjects with the Ile-181-->Leu variant of Fc epsilon RI-beta. 933 44

Stem cell factor (SCF) has a major role in hematopoiesis and in the regulation of mast cell development and function. For example, recombinant human SCF (rhSCF) can induce the development of human mast cells from precursor cells in vitro, stimulate mediator release from human skin mast cells in vitro, and promote both the development and functional activation of human skin mast cells in vivo. In the present study, we used a new ultrastructural enzyme-affinity method, employing diamine oxidase (DAO)-conjugated gold particles (DAO-gold), to detect histamine in skin biopsies obtained from patients with breast carcinomas who were receiving daily subcutaneous (SC) injections of rhSCF in a phase I study of this cytokine. We examined control biopsies obtained at sites remote from rhSCF injection as well as biopsies of rhSCF-injected skin that were obtained within 2 hours and 30 minutes of the SC injection of rhSCF at that site. The rhSCF-injected sites (which clinically exhibited a wheal-and-flare response), but not the control sites, contained mast cells undergoing regulated secretion by granule extrusion. The DAO-gold-affinity method detected histamine in electron-dense granules of mast cells in control and injected skin biopsies; however, the altered matrix of membrane-free, extruded mast cell granules was largely unreactive with DAO-gold. Notably, DAO-gold bound strongly to fibrin deposits and collagen fibers that were adjacent to degranulated mast cells. These findings represent the first morphologic evidence of histamine secretion by classical granule exocytosis in human mast cells in vivo.
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PMID:Diamine oxidase-gold ultrastructural localization of histamine in human skin biopsies containing mast cells stimulated to degranulate in vivo by exposure to recombinant human stem cell factor. 937 68

We performed an ultrastructural analysis of 10 skin biopsy specimens that had been obtained from three women who were undergoing daily subcutaneous dosing with recombinant methionyl-human stem cell factor (rhSCF) as part of a phase I clinical trial. The biopsy specimens were obtained at sites of subcutaneous administration of rhSCF, within approximately 1 to 2 hours of rhSCF injection, and, at the same time, at contralateral control sites that had not been directly injected with rhSCF. We previously reported that subcutaneous dosing with rhSCF in these subjects induced the local development of a wheal and flare response, which was associated with evidence of mast cell degranulation, as well as a systemic increase in numbers of cutaneous mast cells. The present electron microscopic analysis revealed that all biopsies of swollen, erythematous rhSCF-injected sites exhibited anaphylactic degranulation of both mature and immature mast cells, an acute inflammatory response characterized by the migration of neutrophils, basophils (some of which exhibited evidence of piecemeal degranulation), and eosinophils through blood vessel walls into the perivascular and extravascular spaces, and edema and fibrin deposition within the interstitium. By contrast, the control biopsies contained no evidence of mast cell degranulation or acute inflammation. However, both control and rhSCF-injected sites exhibited mast cells that were undergoing granule building and maturation. Thus at the doses tested in these subjects, subcutaneous injection of rhSCF induced anaphylactic-type degranulation of dermal mast cells at the injection site, with an acute inflammatory response that was associated with the recruitment of granulocytes. By contrast, mast cells at sites distant from those directly injected with rhSCF exhibited no evidence of enhanced secretion.
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PMID:Ultrastructural analysis of human skin biopsy specimens from patients receiving recombinant human stem cell factor: subcutaneous injection of rhSCF induces dermal mast cell degranulation and granulocyte recruitment at the injection site. 964 7

The diminishing incidence of parasitic infection in westernised societies has been suggested to result in an increased prevalance of asthma. Asthma is a polygenic disease and genome screens have shown that genes on chromosome 5q31-33 are strongly linked to the disease. The gene for the beta2-adrenoreceptor is located in this region and two polymorphisms have been identified that result in amino acid changes at positions 16 (ArgGly) and 27 (GlnGlu). To determine whether these polymorphisms influence asthma and parasitic infection, a genotype/phenotype study has been performed on a cohort of 126 children from Coche Island in Venezuela. There is a high incidence of asthma on the island and intestinal helminthiasis is endemic. Genotyping for both polymorphisms was carried out by using the polymerase chain reaction and allele-specific oligonucleotide hybridisation. Genotype frequencies in this cohort were consistent with other studies and both polymorphisms were in significant linkage disequilibrium. Individuals who were homozygous for Arg16 had significantly higher levels of specific IgE to Ascaris lumbricoides (P=0.002), significantly higher A. lumbricoides egg counts (P<0.001) and significantly larger wheal sizes following skin-prick testing with A. lumbricoides allergen (P=0.008). There was no association between either polymorphism and total serum IgE or asthma in this population. A combination of mast cell degranulation and the lung migratory phase of A. lumbricoides larvae may result in bronchoconstriction in infected individuals. These results suggest that the Gly 16 allele confers resistance to high levels of parasitic infection in this population. An alternative explanation for the association is that it may be the result of linkage disequilibrium with other genes in the chromosome 5q31-33 region.
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PMID:Association of polymorphisms in the beta2-adrenoreceptor gene with higher levels of parasitic infection. 1032 53

Mast cells and their proteases are thought to participate in the development of skin blisters in various pathological conditions. In this study, suction blistering was used as an experimental model to evaluate the significance of mast cells in blister formation after pre-treatment of normal skin with intradermal injections of 100 microg/ml compound 48/80 (a mast cell degranulator) or with 0.1% capsaicin cream. Tryptic and chymotryptic enzyme activities in blister fluids were measured with sensitive p-nitroanilide substrates. Repeated injections of compound 48/80 once a day on 3 or 5 consecutive days or capsaicin applications 3 times a day for 7 or 10 days were used to induce mast cell degranulation and inflammation in normal skin. Both treatments ultimately led to decreased wheal and erythema reactions before suction blistering, but neither treatment affected the size or formation rate of suction blisters. No suction blister fluids had detectable levels of chymotryptic activity, but blister fluids from bullous pemphigoid, herpes zoster and insect bullous eruption, used as the control, revealed clear chymotryptic activity. In addition, tryptic activity in suction blister fluids was not significantly altered after compound 48/80 and capsaicin pre-treatments. However, if the wheal reaction was induced immediately before suction blistering, a significantly increased rate in blister formation together with increased tryptic activity was found, but, unexpectedly, no chymotryptic activity could be detected in blister fluids. The results show that repeated mast cell degranulation in normal skin has no effect on the formation rate of suction blisters, which developed more rapidly on acutely whealing skin. This is probably due to skin oedema rather than mast cell proteases, since no chymotryptic activity was detected in suction blisters where tryptic activity exhibited high individual variation.
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PMID:Suction blister formation in skin after acute and repeated mast cell degranulation. 1038 14

The background of this study is that 5-HT3 receptor antagonists are reported to have an antipruritic effect in uremic and cholestatic pruritus. Recently, we could not confirm such an effect in healthy subjects under experimental conditions. Therefore, it was the aim of the present study to further evaluate a possible antipruritic effect of a 5-HT3 receptor antagonist (tropisetron) on serotonin- and histamine-induced itch before and after skin mast cell depletion in 10 healthy subjects. The results were compared to serotonin and histamine iontophoresis in non-pretreated and pretreated skin with an orally applied antihistamine (cetirizine). Skin mast cell depletion was performed by iontophoretical application of compound 48/80. Wheals and flares were planimetrically evaluated. Itching and burning sensations were rated on an analog scale over a 24-min period. The test protocol also comprised alloknesis, defined as induction of perifocal itch sensations by a mechanical stimulus. When serotonin was iontophoretically applied after mast cells had been depleted before, oral tropisetron resulted not only in significantly lower whealing, itching and alloknesis but also reduced flares. In contrast, after oral pretreatment with tropisetron histamine-induced reactions before and after mast cell depletion did not significantly change. Our study demonstrates that in this model, tropisetron as a 5-HT3 receptor antagonist does not effect histamine-induced itch but has a measurable effect in serotonin-induced reactions when mast cells were depleted before. From these data evidence now exists why tropisetron is to some extent effective in certain types of pruritus such as uremic pruritus, known for increased histamine liberation and increased serotonin levels as well as degranulated and diffusely spread mast cells in the skin.
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PMID:The antipruritic effect of a 5-HT3 receptor antagonist (tropisetron) is dependent on mast cell depletion--an experimental study. 1043 22

While histamine is the crucial mediator of pruritus in type 1 allergic reactions, its role in atopic dermatitis (AD) is unclear. In this study, the role of mast cell mediators in protein extravasation and pruritus was evaluated using intradermal microdialysis. The microdialysis capillaries were used to apply the mast cell degranulating substance compound 48/80 (C48/80; 0.05%) or histamine (0.01%) and also to deliver H1-blockers (cetirizine, 200 microg mL-1) in nine AD patients and nine controls. Large pore size membranes (3000 kDa) enabled simultaneous analysis of protein extravasation. Itch sensation was measured psychophysically and weal and flare reaction were evaluated planimetrically. Protein extravasation induced by histamine and C48/80 was significantly reduced in AD patients. Blockade of H1-receptors by cetirizine significantly reduced C48/80-induced protein extravasation in AD patients and controls to an identical level. C48/80-induced pruritus was abolished by cetirizine in controls, whereas pruritus in AD patients was unchanged after H1 blockade. We conclude that mast cell mediators others than histamine are involved in C48/80-induced pruritus in AD patients. Whether the reduced capacity of AD patients to induce protein extravasation is of pathophysiological relevance for pruritus remains to be established.
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PMID:Mast cell mediators other than histamine induce pruritus in atopic dermatitis patients: a dermal microdialysis study. 1084 27

1. This study examines the relative contributions made by inhibition of mast cell degranulation, reduction of mast cell recruitment and maturation, and lowering the responsiveness of the vasculature to histamine, in the inhibition by glucocorticoids of the weal and flare in human skin. 2. One forearm of healthy human volunteers was treated for 24 h (n=6) or daily for 21 days (n=10) with 0.05% clobetasol propionate. The other arm served as control. Weal and flare responses were elicited by intradermal injection of 20 microl of 0.3 mM codeine. The areas of the responses were measured using scanning laser Doppler imaging. Microdialysis was used to assess histamine release. Mast cell numbers and tissue histamine content were assessed in 4-mm punch biopsies. Histamine (20 microl of 1 microM i.d.) was used to assess the status of the vasculature. 3. No significant effects were seen at 24 h. At 21 days, clobetasol reduced the areas of the codeine-induced weal and flare responses by 59 and 58% respectively (both P=0.006). Mast cell numbers were reduced by 47%, (P=0.014) and total tissue histamine content by 52% (P=0.006). Codeine-induced histamine release was reduced by 44% (P=0.022). The weal, but not the flare, induced by histamine was significantly inhibited (P=0.019). Echography revealed a 15% thinning of the skin by clobetasol. 4. These results demonstrate that reduction of the weal and flare responses to codeine following clobetasol treatment, results primarily from reduced mast cell numbers and tissue histamine content rather than inhibition by corticosteroids of mast cell degranulation.
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PMID:Inhibition by glucocorticoids of the mast cell-dependent weal and flare response in human skin in vivo. 1115 88


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