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)

In the rat larynx, plasma exudation and edema formation were studied by light and electron microscopy after i.v. injections of the mast cell activator compound 48/80, substance P, and capsaicin. The morphological effects of substance P and capsaicin on connective tissue mast cells in vivo were also examined. Of the drugs tested, only compound 48/80 degranulated the connective tissue mast cells. All drugs induced a subepithelial plasma exudation in the subglottic region, with edema in the lamina propria and widened intraepithelial intercellular spaces, though the tight junction regions seemed intact. In the epiglottis, 10 min after compound 48/80 injection, there was edema in the lamina propria on the lingual side, with an intact and tight epithelial lining. No morphological sign of edema was found in the epiglottis after injection of substance P or capsaicin. The pronounced effect found in the epiglottic region after compound 48/80 injection was due to the release of mediators such as histamine and 5-hydroxytryptamine from the connective tissue mast cells. This study supports the belief that substance P in vivo mediates an increased vascular permeability by a direct effect on the blood vessels - a mechanism distinct from mast cell degranulation.
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PMID:Edema formation in the rat larynx. 956 Apr 79

Bothropstoxin-I and bothropstoxin-II are phospholipase A2 homologues isolated from Bothrops jararacussu snake venom. The former is devoid of phospholipase A2 activity whereas the latter has very low enzymatic activity. In this study, we have investigated the in vivo (rat paw and skin oedema) and in vitro (mast cell degranulation) inflammatory effects caused by bothropstoxin-I and bothropstoxin-II. Bothropstoxin-I (25-100 microg/paw) and bothropstoxin-II (12.5-50 microg/paw) caused dose-dependent rat paw oedema. The intradermal injection of bothropstoxin-I (0.125-5 microg/site) and bothropstoxin-II (0.125-5 microg/site) into rat skin also resulted in dose-dependent oedema formation. These oedematogenic activities were largely reduced in animals pretreated with the histamine/5-hydroxytryptamine (5-HT) receptor antagonist cyproheptadine (2 mg/kg, i.p. 0.5 h before). Similarly, p-bromophenacyl bromide, a compound known to inhibit phospholipase A2 activity, significantly inhibited rat paw and skin oedema induced by both phospholipase A2 homologues. The polyanion heparin (5 IU/site) significantly reduced the rat skin oedema induced by either bothropstoxin-I or bothropstoxin-II as well as the paw oedema (50 IU/site) induced by the former. When assayed in the rat peritoneal mast cells in vitro, both bothropstoxin-I (10 and 100 microg/ml) and bothropstoxin-II (3 and 10 microg/ml) significantly caused [14C]5-HT release. The [14C]5-HT release caused by these phospholipase A2 homologues were reduced by p-bromophenacyl bromide and heparin (50 IU/ml). Our results indicate that oedema formation induced by bothropstoxin-I and bothropstoxin-II is mostly dependent on in vivo mast cell degranulation. Since heparin greatly reduced the oedematogenic activity of these phospholipase A2 homologues, it is likely that the cationic charge of these substances plays a major role in the mast cell activation. Our results also indicate that p-bromophenacyl bromide may not be a suitable pharmacological tool to investigate the correlation between enzymatic activity and the inflammatory effects of phospholipases A2.
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PMID:Mast cell degranulation induced by two phospholipase A2 homologues: dissociation between enzymatic and biological activities. 957 Apr 75

Reverse transcription--polymerase chain reaction of mRNA from rat RBL-2H3 cells yielded a 316 base pair band consistent with that predicted for the neurokinin-1 (NK1) receptor. Saturation and competition binding with 125I-labeled Bolton-Hunter substance P, substance P fragments, and a series of selective tachykinin receptor agonists and antagonists demonstrated that RBL-2H3 cells express high affinity binding sites for substance P on their surfaces with the kinetic and pharmacological properties of NK1 receptors. The pharmacology of these 125I-labeled substance P binding sites was (from most to least potent) [Sar9,Met(O2)11]substance P > substance P 4-11 >> GR82334 << MEN 10,376. However, substance P 1-4, substance P 8-11, substance P 9-11, and [Trp7, beta-Ala8]neurokinin A 4-10 failed to compete for binding. The metabolically stable NK1 receptor agonist, [Sar9,Met(O2)11] substance P, caused a 49% increase in 5-hydroxytryptamine release above basal levels. The results demonstrate the presence of functional NK1 receptors on RBL-2H3 cells, a mucosal-like mast cell line.
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PMID:Presence of NK1 receptors on a mucosal-like mast cell line, RBL-2H3 cells. 963 59

Nociceptin (20 microg/kg i.p.) strongly inhibited cutaneous Evans blue accumulation in the chronically denervated hindpaw of the rat in response to mast cell degranulating peptide (MCDP, 0.25 microg in 100 microl) but it had no and marginal effect on plasma extravasation induced by 5-hydroxytryptamine (5-HT, 0.5 microg in 100 microl) and histamine (0.1 microg in 100 microl), respectively. Release of sensory neuropeptides such as substance P, calcitonin gene-related peptide (CGRP) and somatostatin from the rat isolated trachea in response to capsaicin (10(-8) M) or bradykinin (10(-7) M) were also attenuated by nociceptin (100 and 300 nM). It is concluded that chemically induced discharge of mediators from mast cells and from capsaicin-sensitive afferent nerve terminals are both inhibited by nociceptin that participates in the anti-inflammatory effect of the peptide.
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PMID:Inhibition of nociceptin on sensory neuropeptide release and mast cell-mediated plasma extravasation in rats. 965 Aug 54

Wasp venoms contain several active components, among them kinin-related peptides. Like bradykinin and [Thr6]bradykinin, Vespula vulgaris venom caused paw oedema following subplantar injection in anaesthetized rats. The oedema was partly inhibited by the bradykinin B2 receptor antagonist icatibant (Hoe 140); the remaining part was abolished by additional pretreatment with 5-hydroxytryptamine (5-HT) receptor antagonists or mast cell depletion. Histamine receptor antagonists were ineffective. Capsaicin pretreatment attenuated oedema formation indicating a neurogenic sensory component. Nociceptive behavioural responses induced by the venom in unanaesthetized rats were abolished by icatibant. It is concluded that kinins, either contained in the venom or released from the tissue, play the predominant role in the inflammatory and algesic effects. The inflammatory effects only partly rely on direct, bradykinin receptor-mediated mechanisms while the remaining part depends on the release of 5-HT from skin mast cells. The algesic effects of the venom are entirely due to direct B2 receptor activation.
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PMID:Vespula vulgaris venom: role of kinins and release of 5-hydroxytryptamine from skin mast cells. 969 10

In addition to its neuronal effects, nerve growth factor (NGF) is known to act on inflammatory and immune cells. The aim of the present study was to investigate the effect of colchicine on NGF-induced leukocyte accumulation and thermal hyperalgesia. Initial experiments showed that intradermal injection of recombinant human (rh) NGF (0.8 and 4 microg) caused a longlasting increase in tissue myeloperoxidase (MPO) indicating leukotactic activity of NGF. Colchicine (0.3 and 1 mg/kg) attenuated the NGF (0.8 and 4 microg)-induced increase in tissue myeloperoxidase (MPO) as determined 6 h after NGF application. Intraplantar injection of NGF into the rat hindpaw caused a decrease in thermal nociceptive threshold, which, at 4 microg NGF, was accompanied by moderate (about 35% increase in paw volume) edema. The thermal hyperalgesia was evident 20 min after injection and lasted less than 4 h. Colchicine (0.3 and 1 mg/kg) had no significant effect on NGF-induced edema, but reduced NGF-induced thermal hyperalgesia. Colchicine (1 mg/kg) did not significantly reduce thermal hyperalgesia produced by intraplantar bradykinin, prostaglandin E1, or 5-hydroxytryptamine. Treatment of rats with a dose of indometacin (2 mg/kg) that was sufficient to block cyclooxygenase had no significant effect on NGF-induced thermal hyperalgesia or edema. In vitro, colchicine (0.4-12 microg/ml) did not significantly influence NGF (10 ng/ml)-induced histamine release from rat peritoneal cells, suggesting that a mast cell stabilizing effect of colchicine did not contribute to inhibition of NGF-induced thermal hyperalgesia. The results show that NGF causes localized indometacin-resistant thermal hyperalgesia that can be blocked by the microtubule disrupting agent colchicine. These results raise the possibility that a mechanism by which NGF produces peripheral sensitization is related to its leukotactic effect.
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PMID:Effect of colchicine on nerve growth factor-induced leukocyte accumulation and thermal hyperalgesia in the rat. 975 13

Adenosine may play a role in asthma by enhancing inflammatory mediator release from lung mast cells. In this study, we investigated whether adenosine is released from cultured rat basophilic leukaemia (RBL-2H3) cells in response to antigen challenge and whether released adenosine enhances mediator release. RBL-2H3 cells closely resemble mucosal mast cells, the most common type of mast cell in lung tissue, and they express adenosine A3 receptors (which have been associated with asthma). Measurement of adenosine in RBL-2H3 cell incubation medium was possible if adenosine metabolism was inhibited by EHNA (10 microM; an adenosine deaminase inhibitor) and 5-iodotubericidin (5-IT; 10 microM; an adenosine kinase inhibitor). Basal adenosine concentration increased up to 1.0 microM during a 90 min incubation; after antigen challenge, adenosine concentration was increased by 0.3-0.4 microM above basal. Antigen-induced adenosine release ranged from 30-70 nmol/1.25x10(6) cells. Antigen-induced mediator release (beta-hexosaminidase and [3H]5-hydroxytryptamine) was increased by APNEA, an adenosine A3 receptor agonist (EC50 approximately 20 nm) but inhibited by EHNA and 5-IT, despite increased adenosine levels. This inhibition was not blocked by the adenosine A1/A2 receptor antagonist DPSPX (5 microM). Therefore, it is unlikely to be related to adenosine receptor activation. In conclusion, although our data provide no direct support for a positive feedback effect of adenosine on mast cell mediator release, the observation that IgE receptor stimulation increases adenosine production in cells which express stimulatory A3 receptors is consistent with this hypothesis.
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PMID:Evidence that IgE receptor stimulation increases adenosine release from rat basophilic leukaemia (RBL-2H3) cells. 980 62

The secretion process of the mucosal mast cell line RBL-2H3 was imaged using infrared three photon excitation (3PE) of serotonin (5-hydroxytryptamine, 5-HT) autofluorescence, a measurement previously difficult because of the technical intractability of deep UV optics. Images of prestimulation 5-HT distributions were analyzed in loaded cell populations (those incubated in a 5-HT-rich medium overnight) and in unloaded populations and were found to be strictly quantifiable by comparison with bulk population high-performance liquid chromatography measurements. Antigenically stimulated cells were observed to characteristically ruffle and spread as granular 5-HT disappeared with no detectable granule movement. Individual cells exhibited highly heterogeneous release kinetics, often with quasi-periodic bursts. Neighboring granule disappearances were correlated, indicative of either spatially localized signaling or granule-granule interactions. In one-half of the granule release events, weak residual fluorescence was visible suggestive of leftover 5-HT still bound to the granule matrix. The terminal stages of secretion (>300 s) consisted primarily of unresolved granules and remainder 5-HT leakage from already released granules.
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PMID:Mucosal mast cell secretion processes imaged using three-photon microscopy of 5-hydroxytryptamine autofluorescence. 1009 82

Piratoxin-I (PrTX-I) is a Lys-49 phospholipase (PLA(2)) homologue, isolated from Bothrops pirajai snake venom, that has no phospholipase activity. In this study, we investigated the in vivo oedematogenic activity of PrTX-I in both the rat and the rabbit as well as the ability of PrTX-I to activate rat mast cells in vitro. In the rat paw and skin, PrTX-I (3-100 microg/paw) induced a dose-dependent oedema that was associated with extensive mast cell degranulation. The involvement of mast cells in PrTX-I-mediated oedema formation in the rat was further confirmed by the findings that this protein significantly activated rat peritoneal mast cells in vitro, causing the release of [(14)C]5-hydroxytryptamine ([(14)C]5-HT; 51 +/- 1%). In the rabbit, PrTX-I (10-100 microg/site) also induced dose-dependent skin oedema formation that was not affected by either mepyramine (a histamine H(1) receptor antagonist) or cyproheptadine (1.0 microg/site), indicating that mast cells do not play a role in this animal species. The bradykinin B(2) receptor antagonist Hoe 140 (0.5 microg/site) and the platelet-activating factor (PAF) receptor antagonist WEB 2086 (200 microg/site) also failed to affect the PrTX-I-induced rabbit skin oedema, ruling out the involvement of kinins and PAF. The PLA(2) inhibitor p-bromophenacyl bromide greatly reduced the PrTX-I-induced oedema in both the rat and the rabbit, and also inhibited the rat in vitro mast cell activation induced by this PLA(2) homologue. The polyanions heparin and dermatan sulphate efficiently prevented oedema formation in both species, and heparin inhibited PrTX-I-induced rat mast cell degranulation. Our results are consistent with the suggestion that the cationic charge of PrTX-I plays a major role in the inflammatory responses induced by this PLA(2) homologue.
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PMID:Inflammatory oedema induced by the lys-49 phospholipase A(2) homologue piratoxin-i in the rat and rabbit. Effect of polyanions and p-bromophenacyl bromide. 1073 29

Bothropstoxin-I (BthTX-I) and bothropstoxin-II (BthTX-II) are Lys-49 and Asp-49 phospholipases A(2) (PLA(2)s), respectively, isolated from Bothrops jararacussu venom. Piratoxin-I (PrTX-I) is a Lys-49 PLA(2) isolated from Bothrops pirajai venom. In this study, the ability of BthTX-I, BthTX-II and PrTX-I to recruit leucocytes into the rat pleural cavity and potential mechanisms underlying this effect were investigated. Intrapleural injection of either BthTX-I or PrTX-I (10-100 microg/cavity each) caused a significant leucocyte infiltration at 12 h after injection. The maximal cell migration was observed with the dose of 30 microg/cavity (14.9+/-15.5 and 17.6+/-1. 6x10(6) cells/cavity, respectively). Leucocyte counts consisted mainly of mononuclear cells, but significant amounts of neutrophils and eosinophils were also observed. Intrapleural injection of BthTX-II (10-100 microg/cavity) caused a marked leucocyte infiltration at 6 and 12 h after injection. The maximal response was observed with the dose of 100 microg/cavity (57.3+/-3.4x10(6) cells/cavity, 6 h). The leucocyte counts were mainly composed of neutrophils and mononuclear cells. The treatment of either BthTX-I (30 microg/cavity, 12 h) or BthTX-II (30 microg/cavity, 6 h) with the PLA(2) inhibitor p-bromophenacyl bromide (p-BPB) had no effect on the total and differential leucocyte counts induced by these proteins. The same treatment partially reduced the PrTX-I-induced pleural leucocyte infiltration. In rats depleted of the histamine and 5-hydroxytryptamine (5-HT) stores by chronic treatment with compound 48/80, the total leucocyte counts in response to BthTX-I, BthTX-II and PrTX-I was not significantly affected compared to control animals. In addition, BthTX-I, BthTX-II and PrTX-I (100 microg/ml each) significantly degranulated pleural mast cells in vitro leading to the release of [(14)C]5-hydroxytryptamine ([(14)C]5-HT). p-BPB and heparin (50 IU/ml) significantly reduced the [(14)C]5-HT release induced by these PLA(2)s. Our results demonstrate that BthTX-I, BthTX-II and PrTX-I recruit leucocyte into the pleural cavity of the rat by mechanisms unrelated to enzymatic activity and pleural mast cell degranulation.
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PMID:Leucocyte recruitment induced by type II phospholipases A(2) into the rat pleural cavity. 1085 16


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