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)

Sch 40120 (10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b] [1,8]naphthyridin-5(7H)-one) is an inhibitor of the 5-lipoxygenase enzyme in rat neutrophils, human neutrophils and the the MC9 murine mast cell clone with IC50 values of 8, 4 and 7 microM, respectively. The drug was examined for its effects on acute inflammatory responses in the paw and pleural cavity of rats. The drug suppressed paw inflammation triggered by a reverse passive Arthus reaction or a subplantar injection of the polysaccharide carrageenan with p.o. ED50 values of 0.2 and 1.5 mg/kg, respectively. In reverse passive Arthus reaction and carrageenan pleurisy models, Sch 40120 was found to suppress both the cellular and fluid components of the acute inflammation. The p.o. ED50 values for inhibition of cells and fluid in pleurisy models were in the range of 0.1 to 0.7 mg/kg. When applied locally to the ears of mice, the drug blocked an arachidonic acid-induced and leukotriene-mediated ear inflammation with an ED50 of 0.072 mg/ear. These findings suggest that Sch 40120 is a potent anti-inflammatory agent that may be particularly useful in the treatment of inflammatory diseases such as psoriasis in which leukotrienes appear to be major mediators of the pathological symptoms that characterize the disease state.
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PMID:Actions of a 5-lipoxygenase inhibitor, Sch 40120, on acute inflammatory responses. 138 87

Leukocyte trafficking in normal and diseased skin appears to be initially governed by endothelial surface glycoproteins that promote adhesive interactions with circulating leukocytes. In a separate study, we have demonstrated that one of these glycoproteins, endothelial-leukocyte adhesion molecule-1 (ELAM-1), is rapidly induced on postcapillary dermal venules as a direct consequence of experimentally-elicited degranulation of adjacent mast cells (Proc Natl Acad Sci USA 86:8972-8976, 1989). A principle endogenous mediator of mast cell degranulation is the neuropeptide substance P. In this study, we exposed organ cultures of neonatal human foreskins for 45 min to substance P or to a substance P analogue (D-pro4, D-trp7,9)SP(4-11) that binds to the identical mast cell surface receptor but which does not provoke histamine release. Dermal mast cells were uniformly degranulated only in explants exposed to substance P, as judged by ultrastructural analysis. After subsequent culture in medium alone for 6 h, superficial venules of explants exposed to substance P showed evidence of ELAM-1 induction, as documented histochemically using H4/18 monoclonal antibody. ELAM-1 was not induced by substance P analogue. Furthermore, preincubation of explants with analogue or with the mast cell inhibitor, cromolyn sodium, abrogated the ability of substance P to induce ELAM-1. From these results we suggest that substance P endogenously released by dermal nerve fibers upon physiologic or electrical stimulation may be important in the regulation of endothelial-leukocyte interactions in vivo. This concept provides further evidence for a neurogenic and psychogenic modulation of the immune response, and may be relevant to the course of naturally occurring dermatoses (e.g., psoriasis) that are commonly exacerbated by emotional stress.
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PMID:Substance P induces the expression of an endothelial-leukocyte adhesion molecule by microvascular endothelium. 169 Feb 49

Histamine release from dispersed skin mast cells may be used for functional studies on the mast cell. However, technical difficulties have hampered such studies. In the present study a new fiberglass-based histamine assay was applied to previously described dispersion techniques, using excision biopsies from 7 patients with urticaria pigmentosa, 3 with psoriasis as well as 4 with urticaria. However, sufficient mast cell numbers for performing histamine release could only be obtained from patients with urticaria pigmentosa. The average mast cell yield was 935 +/- 470 cells (mean +/- SD) per mg wet weight of tissue. The skin mast cells from these patients responded with dose-dependent histamine release to anti-IgE, calcium ionophore A23187, and N-formyl-methionyl-leucyl-phenylalanine challenge without previous passive sensitization. The pattern of histamine release of mast cells and corresponding blood basophils did not indicate substantial differences between the two cell types.
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PMID:Histamine release from skin mast cells and basophils in patients with urticaria pigmentosa. 169 Apr 93

The aim of the present study was to test further our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic. For this purpose, contact sites between mast cells and sensory nerves were morphometrically analysed in the basement membrane zone, papillary dermis and three dermal zones of lesional/non-lesional psoriatic and lichen planus skin as well as in healthy control skin. The analyses were made on sections stained with a histochemical double stain developed for this study. With the double stain, active mast cell tryptase was stained blue enzyme histochemically, and the sensory nerves black using specific monoclonal anti-neurofilament antibodies with immunogold. In psoriatic lesions, both mast cells and mast cell--nerve contacts were markedly more frequent in the basement membrane zone and in the papillary dermis when compared with the corresponding areas in the other groups. Mast cell numbers were increased in both lesional and symptom-free skin in lichen planus, but no increase was found in the mast cell--nerve contacts. Increased contacts between mast cells and sensory nerves indicate that the elements exist for neurogenic inflammation in psoriatic lesions. These increased contacts are not due to the extensive inflammatory reaction only, because they were not observed in lichen planus lesions.
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PMID:Quantitative analysis of contact sites between mast cells and sensory nerves in cutaneous psoriasis and lichen planus based on a histochemical double staining technique. 172 96

Two mechanisms have been proposed for the pathogenesis of eruptions induced by angiotensin-converting enzyme (ACE) inhibitors: (1) an allergic, immune-mediated reaction and (2) a pharmacologic, dose-dependent response. Two cases of palmoplantar psoriasis are presented, which can be attributed to the induction (case 1) and exacerbation (case 2) of ACE inhibitors. The first patient developed his eruption 2 months after he had received captopril, probably as a result of an allergic immunologic mechanism. This has been based mainly on circumstantial evidence and is further strengthened by the positive result of the mast cell degranulation test. The second patient developed an atenolol-induced, mild plantar psoriasis. She experienced a dramatic flare-up of her psoriatic lesions shortly after she had received an ACE inhibitor. It is suggested that her reaction occurred as a result of the enalapril-induced augmentation of kinin levels in the skin. These 2 patients represent deductive and unusual examples of the two different mechanisms that are responsible for the cutaneous complications of ACE inhibitors.
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PMID:Psoriasis related to angiotensin-converting enzyme inhibitors. 220 59

Many classes of drugs exert anti-inflammatory activity through mechanisms which affect all or part of the inflammatory process. Some of these agents are beneficial in the practice of dermatology, while others, such as penicillamine, mast cell blockers and serotonin antagonists, find little or no application. Corticosteroids, for example, are nonspecific in their anti-inflammatory effects and remain a mainstay of therapy, despite their side effect profile. Other drugs, such as the non-steroidal anti-inflammatory agents or gold, can be used in the treatment of diseases associated with rheumatic or autoimmune states. Moreover, antihistamines play an important role in the control of itching, but are mainly indicated in controlling non-dermatological allergic sequelae. Interestingly, chloroquine and dapsone, which were originally developed for use in malaria prophylaxis and leprosy, respectively, have value in treating a wide range of dermatological conditions via mechanisms which include the inhibition of P-450 isoenzymes. In diseases characterised by disturbed cornification (e.g. psoriasis pustulosa), retinoids are of particular value. These drugs are thought to act by inhibition of collagenases, proteases and granulocyte migration. Undoubtedly, further investigation of drug classes such as oxygen radical controllers and immunomodulators will clarify their mechanisms and establish their therapeutic usefulness among the anti-inflammatory agents now available for dermatological use.
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PMID:The present status of anti-inflammatory agents in dermatology. 307 31

Mast cell degranulation (MCD) was studied in lesions of chronic psoriasis vulgaris before and during topical treatment with low-strength anthralin. Before the treatment, two forms (A and B) of mast cells with Type I MCD were distinguished in the lesions, in addition to mast cells showing Type II MCD. In Type I MCD, electron-dense mast cell granules in form A mast cells, and electron-dense mast cell granules and vacuoles containing granule matrix in form B mast cells, were released as intact structures by the mechanism of diacytosis. Distinct gaps of the mast cell plasma membranes were observed. Around blood vessels, beneath the epidermal-dermal junction and in the intercellular space of strata basale and spinosum, the mast cell granules appeared partly as intact structures and partly in more or less disintegrated form. In Type II MCD the granule matrix was released into the extracellular compartment by the mechanism of exocytosis. During treatment with low-strength anthralin, the mast cell changes underwent regression. In macular psoriasis only form A mast cells of Type I MCD were demonstrated, and the released intact mast cell granules were restricted to the immediate neighbourhood of the mast cells. There were no mast cell granules in the epidermis. At the sites with clinically complete clearance of psoriatic lesions, the mast cells displayed no degranulation but distinct gaps were still found in the mast cell plasma membranes. Low-strength anthralin's mode of action in psoriasis is suggested to involve regression of a series of systems, including prevention of mast cell degranulation, thereby inhibiting release of histamine, proteinase and other mast cell mediators sustaining the psoriatic process.
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PMID:Mast cell alterations in chronic psoriasis vulgaris: response to low-strength anthralin treatment. A transmission electron microscopic study. 371 18

Clinically normal psoriatic skin (CNPS) and psoriatic lesions (PLs) were studied for mast cell degranulation (MCD) in patients with acute eruptive guttate psoriasis vulgaris (AEGP) following penicillin-treated acute streptococcal throat infection. The clinically manifest duration of psoriasis at the time of the biopsies was 2, 5, 10, 14, or 21 days. Two types of MCD were distinguished. Type I was characteristic for those portions of the CNPS in which vascular and epidermal changes were detected, while the PLs showed both Type I and Type II MCD. In Type I MCD the extruded granules (MCGs) in the immediate vicinity of the mast cells appeared as intact bodies encased in a distinctly trilaminar membrane. Around subepidermal and subpapillary blood vessels, in stratum papillare without proximity of blood vessels, beneath the epidermal-dermal junction, in lamina lucida, and in intercellular space of strata basale and spinosum the MCGs appeared partly as intact structures and partly in more or less disintegrated form. In Type II MCD the MCGs were extruded without perigranular membranes. The data here presented showed that MCD is an early and constant feature in the evolution of AEGP.
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PMID:Mast cell degranulation in the evolution of acute eruptive guttate psoriasis vulgaris. 651 69

A light and electron microscopic study of the evolution of acute eruptive guttate psoriasis vulgaris (AEGP) following penicillin-treated streptococcal throat infection is presented. The earliest recognizable changes, distinguished in clinically normal psoriatic skin (CNPS) from patients with psoriasis of 2 days' duration, comprised mast cell degranulation (Type I MCD), a vascular pattern showing endothelial cell gaps in postcapillary venules and postcapillary venules with endothelial cell hypertrophy and compressed lumen as well as epidermal involvement with punctiform spongiotic areas (PSAs). These early dermal and epidermal changes suggest that Type I MCD represents a primary morphologic event. Inflammatory infiltrate of mononuclear cells and exocytosis of mononuclear cells into the PSAs appeared when the concomitant overt psoriasis was 5-21 days old, and these changes were persistent in psoriatic lesions (PLs) of 2 days' duration. They are suggested to be precursors of overt psoriasis. In 2-day-old PLs, MCD (Types I and II) was a prominent feature. It was associated with (1) more extensive vascular changes, (2) inflammatory infiltrate of mononuclear cells and scanty polymorphonuclear leukocytes, (3) epidermal hyperplasia, and (4) migration of a few polymorphonuclear leukocytes through the epidermis with formation of Munro microabscesses in parakeratotic areas of stratum corneum. From the morphologic viewpoint, the progression from 2-day-old to fully evolved PLs seemed basically to be quantitative. The demonstration of MCD as a salient feature in the evolution of AEGP may have future therapeutic and preventive implications for psoriasis.
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PMID:Dermal and epidermal involvement in the evolution of acute eruptive guttate psoriasis vulgaris. 651 70

This study has examined the influence of age, sex, and site on the numbers of mast cells in normal human skin from 60 healthy Indian volunteers. 5-microns-thick paraffin-embedded sections were stained with 0.001% toluidine blue and the mean number of mast cells per mm3 estimated. Multivariate analysis of variance revealed significant effects of age, site and sex upon mast cell numbers with greater numbers in the facial skin of young females compared with arm skin of young patients of both sexes and older females. Mast cell numbers were also significantly higher in both involved and uninvolved skin of patients with psoriasis in contrast with increased numbers in involved skin only, observed in lichen planus. This is the first report of mast cell density in Indian Caucasian skin.
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PMID:Variation in mast cell numbers in psoriasis and lichen planus: comparisons with normal skin. 687 17


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