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)

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

Oral administration of niacin (nicotinic acid) at pharmacologic doses that reduce serum cholesterol levels induces intense flushing in humans. We have recently shown that the vasodilation following ingestion of niacin is due to the release of prostaglandin (PG) D2. However, the site from which PGD2 is released is not known. It has previously been shown that topical application of methylnicotinate causes local cutaneous erythema. Thus, we investigated whether topical methylnicotinate causes a release of PGD2 locally from skin and the possibility that skin may be a major contributor to the release of PGD2 when niacin is administered by mouth. Topical administration of methylnicotinate (10(-1) M) to the forearms of human volunteers resulted in 58- to 122-times increases in levels of PGD2 and 25- to 33-times increases in levels of the metabolite of PGD2, 9 alpha,11 beta-PGF2, in blood drawn from the antecubital vein draining the treated sites. Increased levels of PGD2 and 9 alpha,11 beta-PGF2 were not found in blood drawn simultaneously from veins in the contralateral arm, indicating that the PGD2 was released from the site of methylnicotinate application. The release of PGD2 in response to topically applied methylnicotinate occurred in a dose-dependent manner over the concentration range of 10(-3) to 10(-1) M. The release of PGD2 was not accompanied by a release of histamine, suggesting that the release of PGD2 was not from the mast cell. Following oral ingestion of niacin, levels of PGD2 in superficial venous blood draining the skin were 14 to 1200 times higher than the level in arterial blood supplying the skin of the same arm. This finding indicates that the skin is a major site from which PGD2 is released following oral ingestion of niacin. These studies thus indicate that the cutaneous vasodilation that occurs following oral administration of niacin is primarily due to a release of PGD2 from a niacin responsive cell that resides in the skin.
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PMID:Identification of skin as a major site of prostaglandin D2 release following oral administration of niacin in humans. 137 50

Physical exercise is a stimulus capable of provoking urticaria and anaphylaxis in certain individuals. The cutaneous manifestations of EIA include erythema, pruritus, and urticarial whealing. Symptoms may also progress to angioedema, laryngeal edema, bronchospasm, and hypotension. Attacks are consistently associated with increases in serum histamine levels, and atopic individuals are more commonly affected. At least two distinct diseases cause EIA, including CU and classic EIA. A variant form of EIA may also exist. CU episodes are induced by increases in body temperature occurring secondary to physical exercise or passive body warming. Classic EIA episodes are induced only by exercise. Further differences between these two disorders include the size of skin lesions and the high frequency of progression to upper airway distress and shock in classic EIA. The manifestations of EIA occur as a result of mast cell degranulation that releases histamine and other mediators into the circulation. An exaggerated cholinergic response to body warming seems to provoke mast cell degranulation in individuals with CU. In classic EIA, exercise acts as a physical stimulus, which through an unknown mechanism provokes mast cell degranulation. The treatment of acute episodes of EIA includes administration of epinephrine and antihistamines, airway maintenance, and cardiovascular support. Prophylactic treatment includes exercise avoidance, abstention from coprecipitating foods and medications, pretreatment with antihistamines and cromolyn, and the induction of tolerance through regular exercise.
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PMID:Exercise-induced anaphylaxis and urticaria. 159 87

The focus of this study on coital allergy is on discussing the basis for and clinical implications of the immunological reactions that mediate allergic reactions to semen. Allergic reactions to antigens in seminal plasma occur in the case of acute systemic hypersensitivity (ACH), localized postcoital allergic seminal vulvovaginitis, and/or hypersensitivity to exogenous allergens in semen. In the few cases (30 cases at present), ACH may manifest itself in generalized urticaria, orbital and vulval edema, vulval and generalized pruritus, bronchospasm, lower abdominal pain, hypotension, and loss of consciousness. There may be a family history of atopy. Symptoms may appear over months or years before reaching a severe level. The usual case is the appearance after the 1st coital act or after a change in coital, genital, or reproductive occasions. It is not specific to a particular male partner. It may be self-limiting. Condom usage or abstinence may lead to abatement. Localized vulvovaginitis may occur simultaneously with ACH or exist alone. The symptoms are local pruritus, burning, swelling, erythema, and urticaria in varying degrees for up to a week and occur during or after coitus. Douching or vulval irrigations may ameliorate symptoms. Misdiagnosis as genital herpes or infective vulvovaginitis may occur in mild cases. Exogenous allergens derived from drugs, food, and other sources presenting in the semen may contribute to hypersensitivity. This is different from reactions to intrinsic components of seminal plasma. Vaginal exposure to chemical products such as soaps or to airborne particles such as pollen may produce allergic responses. Another possibility is that genital candidiasis may produce local Ige antibodies, and PGE2 induced suppression of cell-mediated immunity. The immunological mechanisms are described as type I hypersensitivity reactions with the antigen reacting with reaginic antibodies of the Ige class which are bound to mast cell or circulating basophils. The antigens and the immune reactions are specified. In the clinical diagnosis, the rare acute systemic form is obvious, but the atypical, recurrent, and intractable forms of vulvovaginitis require investigation with skin tests. Treatment may involve artificial insemination for those seeking pregnancy, immunotherapy, or antihistamines, rather than use of a condom or abstinence.
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PMID:Allergy to coitus. 168

Acute ultraviolet light B (UVB) injury is associated with dermal mast cell histamine release. The possibility that histamine-stimulated prostaglandin (PG) synthesis could be a mechanism for irradiation erythema was therefore examined using human skin explants. Explants responded to UV irradiation (120 mJ/cm2) with a fivefold increase in synthesis of prostaglandins E2, F2 alpha and 6-keto PGF1 alpha. Incubating explants with the H1 antihistamines brompheniramine (50 microM) or pyrilamine (30 microM) inhibited PG release from irradiated explants 63 +/- 4.9% (mean +/- SEM) 6 h after UV exposure. Antihistamines did not affect PG synthesis in control explants. Irradiation increased the histamine concentration in explant conditioned medium only 50% over basal values, suggesting that irradiation enhanced histamine responsiveness. Explants were therefore incubated with exogenous histamine. In irradiated explants, PG synthesis was stimulated threefold by 3 microM histamine. Unirradiated explants' PG synthesis was unaffected by histamine. Enhanced histamine sensitivity was also examined in epidermal cell cultures. In irradiated cultures, histamine sensitivity was again markedly potentiated: as little as 1 microM histamine stimulated significant PGE2 release and the response to 10-30 microM histamine was increased six to eight times compared with that of unirradiated cultures. These studies demonstrate that endogenous histamine stimulates PG synthesis in human skin after UV injury by potentiation of histamine-induced prostaglandin release. Potentiated agonist responses induced by UV exposure may contribute to the effects of UVB irradiation injury and in particular to irradiation erythema.
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PMID:Enhanced prostaglandin synthesis after ultraviolet injury is mediated by endogenous histamine stimulation. A mechanism for irradiation erythema. 169 89

In 12 healthy volunteers the topical application of monoethyl fumarate caused a spontaneous persistent erythema. Systemic application induced flush. In urticaria pigmentosa the influence was significant higher than in normal skin. This fact suggests a mast cell degranulation caused by monoethyl fumarate.
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PMID:[Persistent spontaneous erythema caused by topical use of fumaric acid monoethyl ester--an obligate mast cell degranulation?]. 219 49

The responses of normal skin to ultraviolet (UV) irradiation are an example of inflammation. The chromophores initiating the reaction are unknown. Characteristic clinical findings are erythema, heat, swelling, and pain. Histopathologic changes include epidermal keratinocyte damage with Langerhans cell depletion and dermal edema, endothelial swelling, mast cell degranulation, and cellular infiltration with neutrophils and monocytes. Biochemical changes include release of histamine, cyclo-oxygenase, and lipoxygenase-derived products of arachidonic acid, kinins, and cytokines, probably from a range of epidermal and dermal cell types. These substances very likely assist in mediation of the reaction. The response is more pronounced in young subjects. UVB (280 to 315 nm) and UVA (315 to 400 nm) radiation both produce inflammation, but with marked qualitative and quantitative differences. UVB having more effect on the epidermis, UVA more on the dermis.
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PMID:Acute effects of ultraviolet radiation on the skin. 220 37

A case of localized heat urticaria in a 70-year-old woman is reported. Increased plasma levels of prostaglandin D2 and blood histamine after heat challenge indicate a role for mast cell degranulation in the pathophysiology of the syndrome. Treatment with astemizole increased the temperature threshold to wealing, but not to itch or erythema. The patient was partially desensitized by repeated exposure to heat and this was further improved by indomethacin. After treatment there was no increase in plasma prostaglandin D2 on challenge. No evidence was found for the activation of the alternative complement pathway.
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PMID:Release of prostaglandin D2 and histamine in a case of localized heat urticaria, and effect of treatments. 243 16

The porphyrias are the only group of diseases caused by endogenous phototoxic agents. While patients with erythropoietic protoporphyria and those with porphyria cutanea tarda both have skin lesions on sun-exposed areas, there are differences in their cutaneous manifestations. Based on information discussed in this chapter, the following pathophysiologic mechanisms can be proposed. In porphyria cutanea tarda, photoactivation of the complement system in the presence of uroporphyrin results in activation of dermal mast cells, which release their proteases. This results in dermal-epidermal separation, reflected clinically as skin fragility and vesicles. The interaction between activated mast cells with fibroblasts, the nature of which is still unclear, may contribute to fibrosis and sclerodermoid skin changes. The stimulatory effect of uroporphyrin on collagen biosynthesis by fibroblasts, which occurs independent of irradiation, may be responsible for the sclerodermoid lesions seen at sun-exposed as well as sun-protected areas. In erythropoietic protoporphyria, mast cell activation can occur as the result of complement activation induced by protoporphyrin and irradiation. Protoporphyrin and irradiation may also directly induce the release of preformed and generated mediators from mast cells, a process mediated at least in part by peroxidation. The release of mast cell mediators may account for the erythema, edema, and urticaria observed in patients with erythropoietic protoporphyria upon exposure to sunlight. Interaction of mast cells with fibroblasts, and the direct membrane-damaging effect of protoporphyrin and irradiation on the latter, may contribute to the waxy thickening of skin seen in chronically sun-exposed areas of these patients. There are, however, many unanswered questions. What accounts for the different biological effects of mast cell-derived mediators: dermal-epidermal separation in one, erythema and urticaria in the other? The fragmentation of dermal collagen bundles associated with cleavage beneath the lamina densa, and the hyperpigmentation and hypertrichosis observed in some patients with porphyria cutanea tarda remain unexplained. What is the mechanism of the reduplication of blood vessel basal lamina in the non-sun-exposed areas of both types of patient? Are there any roles for cytokines and epidermal cell-derived eicosanoids? While it is clear that the pathogenesis of cutaneous lesions in porphyria cutanea tarda and erythropoietic protoporphyria involves interactions among inflammatory mediators and various cells in skin, much still needs to be done to further our understanding of their pathophysiology.
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PMID:Mechanisms of phototoxicity in porphyria cutanea tarda and erythropoietic protoporphyria. 248 74

Thermographic analysis of the skin of the forearm of normal men submitted to nasal instillation of 1 ml of a solution of 48/80, 1 X 10(-2), demonstrates that the skin vessels undergo local vasodilatation. Erythema and wheals sometimes appear, due to the stimulation of the dermal mast cells. Mast cells of the nasal mucosa are never stimulated by such instillation. The differences between dermal and nasal mast cell reactions are in accordance with the concept of mast cell heterogeneity.
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PMID:[Mast cell heterogeneity in normal man]. 294 29


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