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)

Tissue from 134 patients with neurodermatitis and prurigo, pseudoepitheliomatous hyperplasia, pemphigus, and urticaria pigmentosa was examined qualitatively for epidermal mast cells. Epidermal mast cells were found in all of the diseases that were studied except dermatitis herpetiformis. Pemphigus vegetans and dermatitis vegetans were frequently associated with the presence of epidermal mast cells. In other pseudoepitheliomatous diseases, such as tuberculosis verrucosa cutis, blastomycosis, and bromoderma, epidermal mast cells were present in many cases. Four of eight patients with acral dermatitis with elevated IgE blood levels had intraepidermal mast cells; the number was much lower in patients with usual neurodermatitis and prurigo nodularis. Only two of ten cases of alopecia mucinosa showed epidermal mast cells. A single epidermal mast cell was found in ten cases of urticaria pigmentosa. Chronic inflammation associated with epidermal cell proliferation appeared to correlate with the presence of epidermal mast cell.
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PMID:Epidermal mast cells. 83 93

The complement system represents an important nonspecific skin defense mechanism. Its activation leads to the generation of products that not only help to maintain normal host defenses but also mediate inflammation and tissue injury. Proinflammatory products of complement include large fragments of C3 with opsonic and cell-stimulatory activities (C3b and C3bi), low molecular weight anaphylatoxins (C3a, C4a, and C5a), and membrane attack complex. Among them C5a or its degradation product C5a des Arg seems to be the most important mediator because it exerts a potent chemotactic effect on inflammatory cells. Intradermal administration of C5a anaphylatoxin induces skin changes quite similar to those observed in cutaneous hypersensitivity vasculitis that occurs through immune complex-mediated complement activation. Complement activation is involved in the pathogenesis of the inflammatory changes in autoimmune bullous dermatoses. In pemphigus complement activation by pemphigus antibody in the epidermis seems to be responsible for the development of characteristic inflammatory changes termed eosinophilic spongiosis. In bullous pemphigoid (BP) interaction of basement membrane zone antigen and BP antibody leads to complement activation that seems to be related to leukocytes lining the dermoepidermal junction. Resultant anaphylatoxins not only activate the infiltrating leukocytes but also induce mast cell degranulation which facilitates dermoepidermal separation and eosinophil infiltration. Similar complement activation seems to play a more direct role in the dermoepidermal separation noted in epidermolysis bullosa acquisita and herpes gestationis. Anaphylatoxin generation via the alternative pathway activation under light irradiation is implicated in the development of the immediate erythematous phototoxic reactions induced by such well-known chemicals as porphyrin, chlorothiazide, demethylchlortetracycline, and chlorpromazine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of complement-derived mediators in inflammatory skin diseases. 128 51

Several skin diseases may present as vesicles or bullae. Immunofluorescent studies are very helpful in differentiating the various disease entities. Familiarity with the procedure and the various kinds of patterns that are specific and non-specific is essential for the practicing dermatologist. Immunofluorescent patterns are particularly helpful in differentiating pemphigus, bullous pemphigoid, cicatrical pemphigoid, herpes gestationis, dermatitis herpetiformis, linear IgA dermatosis and porphyria. Immunofluorescent studies of the skin and sera of these patients were vital to an understanding their pathogenesis. Immunoelectron microscopy has further helped in delineating the exact sites of immunoglobulin deposition, and, thus, identifying the location of the antigens. In pemphigus, studies at the molecular level reveal that the basic pathological process is mediated by an anti-cellular cement substance antibody. The binding of this antibody at the cell surface level results in a process that is seen at the light microscopy level in the form of acantholysis. In bullous pemphigoid cells may play an important role. It appears that the mast cell, eosinophil, and the lymphocyte in harmony with the polymorphonuclear leucocyte work together to bring about an enzymatic degradation of the basement membrane. The specific role of the anti-basement membrane zone antibody is also under current study. With advances in molecular immunology, especially monoclonal antibodies and gene technology, it is hoped that these cellular and molecular interactions will be better understood and further defined.
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PMID:Diagnosis of bullous disease and studies in the pathogenesis of blister formation using immunopathological techniques. 638 5

The possible involvement of mast cell tryptase and chymase in subepidermal bullous diseases was studied enzyme-histochemically in specimens from erythematous and vesicular skin and from non-involved skin of patients with dermatitis herpetiformis, bullous pemphigoid, erythema multiforme, infective bullous eruption and linear IgA dermatosis. Patients with pemphigus were biopsied for comparison. The immunoreactivity of chymase inhibitors, alpha1-proteinase inhibitor (alpha1-PI) and alpha1-antichymotrypsin (alpha1-AC), in mast cells was demonstrated using the sequential double staining method. Tryptase-positive mast cells were unchanged or only slightly increased in number in erythematous lesions and slightly decreased in blistering skin compared with healthy-looking skin. Only occasionally were mast cells seen in apparent contact with the basement membrane zone. Chymase-positive mast cells and the chymase/tryptase ratio steadily decreased during the development of the lesions in each subepidermal bullous disease. The percentage of alpha1-PI+ and/or alpha1-AC+ mast cells increased simultaneously, which could explain the disappearance of chymase activity. Similar results were obtained regardless of the bullous disease. The results were also similar in pemphigus, which is an intraepidermal bullous disease. In conclusion, these results show significant alterations in mast cell chymase and protease inhibitors in a range of different bullous diseases, suggesting mast cell involvement. The apparent inactivation of chymase could be due to the action of chymase inhibitors detected in numerous mast cells. However, these alterations probably reflect general inflammation rather than a specific reaction in a certain bullous disease.
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PMID:Mast cells in developing subepidermal bullous diseases: emphasis on tryptase, chymase and protease inhibitors. 1049 9

Bullous pemphigoid was first described by Lever in 1953 as a subepidermal blistering disease. Its immunohistological features include dermal-epidermal junction separation, an inflammatory cell infiltrate in the upper dermis, and basement membrane zone-bound autoantibodies. These autoantibodies show a linear staining at the dermal-epidermal junction, activate complement, and recognize two major hemidesmosomal antigens, BP230 (BPAG1) and BP180 (BPAG2 or type XVII collagen). An IgG passive transfer mouse model of BP was developed by administering rabbit antimurine BP180 antibodies to neonatal mice. This model recapitulates the key features of human bullous pemphigus. Using this in vivo model system, several key cellular and molecular events leading to the bullous pemphigus disease phenotype were identified, including IgG binding, complement activation, mast cell degranulation, and neutrophil infiltration and activation. Proteinases and reactive oxygen species released by neutrophils work together to damage the basement membrane zone, causing dermal-epidermal junction separation. Recent experimental data from human bullous pemphigus studies suggest that human bullous pemphigus and its mouse IgG passive transfer model counterpart may well share not only common immunohistological features but also pathological mechanisms underlying the development of this antibody-mediated disease.
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PMID:Bullous pemphigoid: using animal models to study the immunopathology. 1487 Sep 84

The skin is a common target of cellular and/or antibody mediated pathological immune responses. Pemphigoids, pemphigus vulgaris and dermatitis herpetiformis are bullous disease due to autoantibodies targeting specific proteins of the skin. The pemphigoid autoantigens are the BP180 and the BP230 antigens, two components of the epithelial basement membrane zone. Additional antigenic targets reported in a portion of patients are laminin 5, the alpha6 subunit of the hemidesmosomal integrin alpha6beta4 and a glycoprotein termed p200. The epidermal and mucosal epithelial cells detachment (acantholysis) characteristic of pemphigus vulgaris is induced by autoantibodies directed against the desmoglein 3 and 1. The desmogleins are desmosomal cadherins, which play a major role in the cell-to-cell adhesion. Dermatitis herpetiformis is regarded as cutaneous phenotype of coeliac disease. A novel autoimmune hypothesis of coeliac disease links wheat gliadin and tissue transglutaminase (TG2) in the gut, which leads to T cell response and IgA autoantibody formation. In dermatitis herpetiformis skin the target for IgA deposition seems to be epidermal TG3. Urticaria is a complex syndrome caused by both immune and non-immune mechanisms. In a subsets of patients with chronic urticaria mast cell degranulation is induced by autoantibodies directed against the a-subunit of the high-affinity IgE receptor, and/or the IgE.
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PMID:New insights into the autoantibody-mediated mechanisms of autoimmune bullous diseases and urticaria. 1646 21