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 efficacy of cetirizine in comparison with meclizine, another piperazine H1 receptor antagonist, in rat pleurisy caused by allergen or autacoid was investigated. Sensitization was achieved by subcutaneous injection of a mixture of ovalbumin and aluminium hydroxide. Fourteen days later, the animals were challenged with an intrathoracic injection of ovalbumin (12 micrograms/cavity), which caused drastic mast cell degranulation, followed by pleural oedema and leucocyte influx. Cetirizine and meclizine (2.5-30 mg/kg i.p.), 1 h before challenge, inhibited the exudatory response evoked by antigen, under conditions where neutrophil and eosinophil accumulation was affected only by the former. When administered intrathoracically 22 h after allergen, i.e. using a curative approach, cetirizine (15 micrograms/cavity) drastically reduced the pleural eosinophilia noted 24 h post-challenge, indicating that this drug can reverse an already established eosinophilia. Cetirizine (15 mg/kg i.p.) also restored, to about 39% (P < 0.001), the number of uninjured mast cells recovered from the pleural cavity following allergen stimulation. In normal rats, cetirizine (5-15 micrograms/cavity) completely inhibited the pleural exudation elicited by histamine and only partially the exudation caused by 5-hydroxytryptamine or bradykinin, but was quite inactive against platelet-activating factor. We conclude that the pleural exudation triggered by allergen, vasoactive amines or bradykinin is clearly sensitive to cetirizine. In addition, the ability of the drug to interfere with pleural neutrophil or eosinophil mobilization and mast cell degranulation seems not to be associated with its ability to block the histamine H1 receptor.
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PMID:Suppression by cetirizine of pleurisy triggered by antigen in actively sensitized rats. 136 60

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

Alterations in the local mast cell population and the eosinophil accumulation in the rat pleural cavity were studied using pleurisy induced by compound 48/80, a standard mast-cell-degranulating agent. Twenty-four hours after the intrathoracic injection of compound 48/80 (1-50 micrograms/cavity), a dose-dependent eosinophil enrichment of the exudate was noted, concomitantly with a drastic reduction in the total number of undamaged mast cells recovered from the pleural washing. At 24 h, neutrophil counts were not modified, and the number of mononuclear cells was increased, but only at the highest dose of compound 48/80. The temporal analysis showed that mast cell degranulation, exudation and neutrophil infiltration were maximal at the interval of 1-6 h after compound 48/80 (25 micrograms/cavity), whereas eosinophil accumulation peaked within 24 h, persisting elevated at least until 96 h. Since compound 48/80 was itself unable to induce eosinophil migration in vitro, attempts were made to investigate the potential involvement of recognized eosinophil chemo-attractants, such as histamine, leukotriene B4 (LTB4) and platelet-activating factor (PAF-acether). The intraperitoneal pretreatment with either cyproheptadine (2 mg/kg), meclizine (40 mg/kg), BW755C (25 mg/kg) or with the PAF-acether receptor antagonist WEB 2086 (20 mg/kg) had no effect on the eosinophil recruitment induced by compound 48/80 (25 micrograms/cavity). However, the treatment with the corticosteroid dexamethasone or the local inhibition of protein biosynthesis with cycloheximide (0.04-200 nmol/cavity) blocked the eosinophil pleural accumulation, but not the mast cell degranulation induced by compound 48/80. Our findings indicate that the pleural eosinophil accumulation induced by compound 48/80 is sensitive to dexamethasone, requires local protein biosynthesis and is independent of histamine, LTB4 and PAF-acether.
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PMID:Eosinophil accumulation in the rat pleural cavity after mast cell stimulation with compound 48/80 involves protein synthesis and is selectively suppressed by dexamethasone. 208 76

This study was undertaken to characterize the different phases of the allergic pleurisy induced by ovalbumin in actively sensitized rats. The reaction was triggered by the intrathoracic injection of ovalbumin (12 micrograms/cavity) into animals sensitized 14 days before. The challenge caused, at 30 min, a drastic mast cell degranulation and exudation which peaked within 4 h. At this time, an intense pleural leucocyte recruitment also occurred, accounted for by an increase in the mononuclear cell counts and by a predominant influx of neutrophils. After 24 h, the mast cell counts started to recover, accompanied by a long-lasting (96 h) accumulation of pleural eosinophils. Forty-eight hours later, the exudation and neutrophils were at basal levels, whereas mast cell counts increased progressively to reach control values at 120 h. This study describes the time course of the exudative and cellular alterations observed during pleural inflammation induced by low antigen concentrations.
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PMID:Kinetics of pleural exudation and cellular alterations induced by antigen in actively sensitized rats. 210 27

Injection of zymosan in rat pleural cavity provokes an exudate which is already detectable at 15 min and which is maximum at 24 h. The leucocyte count (mostly neutrophils) increases at 2-4 h and is maximum at 48 h. In this paper the reaction has been studied up to 6 h. Evidence of histamine release, of mast cell degranulation and of reduction of the exudate by anti-H1 compounds, as well as by sodium cromoglycate, proves the active role played by histamine in the early stage of pleurisy. Serotonin (whose role was studied exclusively using antagonists) seems to have only a minor part in the early phase of the reaction. Some metabolites of arachidonic acid were determined in the pleural exudate at 1 h and 6 h. The concentration of leukotriene B4 was high at 1 h and decreased at 6 h. The thromboxane B2 level was already high at 1 h and was neatly augmented at 6 h while the amount of prostaglandin F1 alpha was high at both times. The non-steroidal anti-inflammatory substances studied all reduced the pleural exudate at 1 h but their activity then varied from each other at 6 h. Cyclooxygenase and lipoxygenase inhibitors (phenidone, BW755C) induced a reduction of the exudate at both times. Zymosan-induced pleurisy seemed thus to be an excellent model for the investigation of antiallergic and anti-inflammatory compounds active on histamine and cyclooxygenase and lipoxygenase pathways.
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PMID:Pharmacological studies on zymosan inflammation in rats and mice. 2: Zymosan-induced pleurisy in rats. 277 57

The inflammatory responses induced by the synthetic polycation poly-L-arginine injected either into the pleural cavity or into the trachea in rats have been investigated. Poly-L-arginine (4-40 nmol/rat) injected intrapleurally induced exudate formation and leucocyte migration (mainly polymorphonuclear cells). The exudate formation (but not cell migration) was dependent on the molecular weight of the poly-L-arginine used (24 and 115 kD). The poly-L-arginine-induced pleurisy was mainly dependent on activation of mast cells since it was significantly reduced either in rats depleted of their stores of histamine and serotonin or in rats previously treated with the serotonin receptor antagonist methysergide. The polyanions heparin and dermatan sulphate when administered intrapleurally with the polycation markedly reduced the exudate formation. Poly-L-arginine (115 kD, 8.5 nmol/rat) injected intratracheally caused lung oedema, increased leucocyte number and protein content of bronchoalveolar lavage, respiratory insufficiency and 60% mortality in 6 h. Depletion of histamine and serotonin stores or of circulating neutrophils decreased the leucocytes in bronchoalveolar lavage but did not increase survival rate, whereas the polyanion dermatan sulphate prevented the mortality completely. These results suggest that the inflammatory changes caused by poly-L-arginine are dependent on mast cell activation but that the lethality after intratracheal administration is due to electrostatic interactions of the polycation with anionic surfaces present in the pulmonary epithelium.
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PMID:Inflammatory responses induced by poly-L-arginine in rat lungs in vivo. 830 37

1. Recent evidence has implicated eosinophils in the inhibition of allergen-induced rat pleurisy, but the mechanism of this negative modulation is not completely understood. This study was undertaken in order to define the potential role of prostaglandins in this phenomenon. 2. Wistar rats were actively sensitized by subcutaneous injection of a mixture of ovalbumin and AI(OH)3 and challenged with an intrapleural (i.pl.) injection of ovalbumin (12 micrograms/cavity) 14 days later. 3. Analysis of the pleural fluid effluent revealed a massive mast cell degranulation and plasma protein extravasation 4 h post-challenge. We confirmed that concurrently with selective pleural fluid eosinophilia caused by platelet-activating factor (PAF), the pleural cavity became hyporesponsive to allergen-induced protein exudation and to the parallel reduction in the number of intact mast cells. 4. These hyporesponsive animals presented a significant augmentation in the pleural effluent level of prostaglandin E2 (PGE2), which increased with increasing numbers of eosinophils in the pleural cavity. Furthermore, pretreatment with either indomethacin or aspirin failed to modify allergen-induced exudation but reversed the exudatory hyporesponsiveness associated with eosinophil recruitment. 5. Allergic exudation was clearly down-regulated by the following pretreatments: (i) PGE2 (10 micrograms/cavity, i.pl.) plus rolipram (40 micrograms/cavity, i.pl.), (ii) misoprostol (200 micrograms kg-1, p.o.) or (iii) dibutyryl cyclic AMP (80 micrograms/cavity, i.pl.). 6. We conclude that prostaglandins may be implicated in the eosinophil-mediated inhibition of allergic pleurisy, probably acting via cyclic AMP signalling pathway activation.
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PMID:Involvement of prostaglandins in the down-regulation of allergic plasma leakage observed in rats undergoing pleural eosinophilia. 886 61

The identity of the histamine-potentiating activity detected in the rat anaphylactic pleural washing was investigated. Wistar rats of both sexes, weighing 150-200 g, were sensitized by injecting subcutaneously (sc) a mixture of ovalbumin and Al(OH)3 14 days before allergen challenge. In sensitized rats, intrapleural (ipl) injection of ovalbumin (12 micrograms/cavity) caused an intense protein exudation. A single ipl administration of compound 48/80 (12 micrograms/cavity) exhausted the resident mast cell population and turned the pleural cavity hyporeactive to the allergen challenge performed 5 days later. Allergen-induced exudation occurred in parallel to a dramatic decrease in the amount of cell-stored histamine (from 9.6 +/- 1.4 (N = 8) to 1.3 +/- 0.1 (N = 6) micrograms/cavity, P < 0.001) in the pleural fluid within 10 min. The anaphylactic cell-free pleural washing obtained at this time, as well as histamine at a concentration equivalent to that stored in pleural mast cells (10 micrograms/cavity), did not induce pleural exudation when injected into normal rats. In contrast, the combined administration of histamine and anaphylactic pleural washing led to remarkable pleural exudation, comparable to that obtained with a high dose of histamine (200 micrograms/cavity) alone. It is noteworthy that the anaphylactic washing from compound 48/80-pretreated rats failed to synergize with histamine. Also, synergism was not reproduced when recipient rats were pretreated with methysergide (50 micrograms/cavity). Consistently, serotonin (5 micrograms/cavity) acted synergistically with histamine (10 micrograms/cavity), producing a greater exudative response than observed with the sum of the effects of each vasoactive amine alone. The results indicate that serotonin accounts for the histamine-potentiating activity noted in the anaphylactic pleural washing, confirming that the synergistic interaction between these vasoactive amines plays a critical role in the rat allergic pleurisy.
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PMID:Histamine-potentiating activity in rat anaphylactic pleural fluid: role of serotonin. 918 Oct 89

1. Bradykinin is suggested to play a role in the pathophysiology of several acute and chronic diseases, including allergic disorders such as asthma. In the present study, we have investigated the importance of bradykinin in mediating allergic inflammation in rats. 2. To this end we have tested the effects of the B2 receptor antagonists Hoe 140, FR173657 or FR172357 on the pleural inflammatory response triggered by intrapleural (i.pl.) injection of allergen (ovalbumin, 12 microg cavity(-1)) in 14 day-actively sensitized Wistar rats. Analysis of the pleural fluid effluent revealed a sequence of mast cell-dependent inflammatory events, including early protein exudation and neutrophilia and late pleural eosinophil influx. 3. Local treatment with Hoe 140 (0.1 and 1 microg cavity(-1)), FR173657 (1 and 10 microg cavity(-1)) or FR172357 (1 and 10 microg cavity(-1)) inhibited dose-dependently allergen-induced mast cell activation with impairment of pleural plasma leakage, neutrophil accumulation and late eosinophil influx. 4. Moreover, the B2 receptor antagonists also dose-dependently inhibited the allergic like inflammatory pleurisy triggered by bradykinin (50 microg cavity(-1)), which is characterized by acute mast cell degranulation, protein leakage and pleural eosinophil infiltration. 5. Taken together, our findings provide substantial evidence to suggest that bradykinin acting on its B2 receptors play a critical role in mediating allergic mast cell-dependent inflammation in rats, and suggest that B2 receptor antagonists may be useful therapeutically to control allergic dysfunction.
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PMID:Suppressive effect of distinct bradykinin B2 receptor antagonist on allergen-evoked exudation and leukocyte infiltration in sensitized rats. 1038 28

To determine the role of mast cells in the recruitment of neutrophils and eosinophils, acute nonspecific pleurisy was induced by injecting isologous serum into normal +/+ and mast cell-deficient Ws/Ws rats. In +/+ rats, neutrophil infiltration peaked 4 h after serum administration, followed by influx of eosinophils after 24-48 h. The levels of neutrophil influx after 4 h as well as the activity of myeloperoxidase (MPO) in pleural lavage-cell extract were significantly lower in Ws/Ws rats than in +/+ rats. In contrast, numbers of eosinophils as well as activity of eosinophil peroxidase (EPO) did not differ significantly between Ws/Ws and +/+ rats. For local reconstitution of mast cells, +/+ rat peritoneal mast cells (PMC) or mesenteric lymph node cells (MLNC) as a control were transferred into the Ws/ Ws pleural cavity. Serum injection into animals with PMC transfer 7 days previously triggered augmented neutrophil influx by approximately 4.7-fold as compared to that in MLNC-transferred animals. Mast cells recovered from the pleural cavity of PMC-transferred rats showed histamine contents equivalent to 20% of that of freshly isolated PMC and retained the reactivity to compound 48/80. These results indicated that dependency of neutrophil recruitment on resident mast cells is greater than that of eosinophils in isologous serum-induced pleurisy.
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PMID:Migration of neutrophils is dependent on mast cells in nonspecific pleurisy in rats. 1054 90


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