Inhibitory effect of interleukin-2 on histamine release from rat mast cells

Interleukin-2 (IL-2) inhibited histamine release from rat mast cells induced by compound 48/80 in a concentration-dependent manner. The inhibitory effect of IL-2 on histamine release was also dependent on the length of the incubation period; the maximum inhibition was achieved at 8 h after IL-2 addition. Furthermore, IL-2 inhibited not only IP₃ production but also⁴⁵Ca uptake in mast cells stimulated by compound 48/80. Since IL-2 enhanced [³H]-leucine uptake into mast cells, this suggests that protein synthesis may be related in some way with the inhibition of histamine release. IL-2 treatment augmented the synthesis of a protein having a molecular weight of approximately 35 kDa. From Western blotting analysis, it became clear that the production of lipocortin-I was augmented in rat mast cells by IL-2 treatment. The present study shows that IL-2 induces the synthesis of lipocortin-I in mast cells and that lipocortin-I may play some role in inhibiting histamine release from mast cells.     

Inhibitory effect of phloretin on histamine release from isolated rat mast cells

The ability of the flavonoid phloretin to inhibit histamine release from rat mast cells varied considerably with the releasing agent investigated. The response to the combination of the ionophore A23187 and the phorbol ester TPA and to suboptimal concentrations of the ionophore (0.5 M) was potently inhibited (IC₅₀ about 5 M), whereas phloretin was less potent against responses to the ionophore (1 M) IC₅₀ of 17 M), to antigen alone and in combination with TPA (IC₅₀ of 30–50 M), to TPA in the absence of calcium (IC₅₀ of 50 M) and to compound 48/80 in the absence and presence of calcium (IC₅₀ of 60–90 M). The inhibition by phloretin at concentrations above 10M was partly counteracted by glucose (5 mM) indicating effects on oxidative metabolism. The flavonoid quercetin was equally potent in inhibiting histamine release induced by antigen, the ionophore at different concentrations and in combination with TPA (IC₅₀ of 20M). Although not conclusive, the results are consistent with an inhibition of protein kinase C by phloretin at concentrations below 10 M. At higher concentrations unspecific actions become apparent and phloretin therefore seems to be of limited utility as a probe for signal-pathways in cell responses.     

Inhibitory effect of lysophosphatidylcholine on the histamine release from rat peritoneal mast cells

Histamine release from isolated rat peritoneal mast cells induced by compound 48/80 (0.5 g/ml) or antigen-antibody reaction was inhibited by lysophosphatidylcholine in a dose-dependent fashion at concentrations up to 4 M. Within the same range of concentration, lysophosphatidylcholine exhibited a membrane-stabilizing action on the model membrane systems decreasing the permeability of lipid bilayer and the fluidity of liposomal membrane in the liquid crystalline state. At concentrations higher than 8 M, lysophosphatidylcholine damaged the cell membrane and subsequently histamine was released. It was assumed that lysophosphatidylcholine may act as an endogenous membrane stabilizer inhibiting histamine release in normal mast cells.     

Anthracycline-induced histamine release from rat mast cells

Comparisons were made of the ability of doxorubicin, daunorubicin, rubidazone and aclacinomycin A to release histamine from rat peritoneal mast cells. Preliminaryin vitro experiments indicated that doxorubicin (10^–6 to 2.5×10^–4 M), in contrast to compound 48/80 and the calcium inophore A23187, did not produce significant release under any condition tested when purified or unpurified rat mast cells were used. Inin vivo experiments, released histamine was measured in the cell-free supernatant of peritoneal fluid of rats after intraperitoneal injection of the agents. The time course of doxorubicin-induced histamine release from the peritoneum was rapid, with maximal release occurring within 4 to 6 min. Dose-response curves of the 4 agents over the range 10^–5 to 3.3×10^–3 M revealed that all caused histamine release, with 10^–3 M concentrations of each causing maximal release of comparable magnitude to that produced by 9.5×10^–6 M A23187. Treated mast cells recovered from the peritoneal cavity showed degranulation and vacuolization when examined by electron microscopy. Increased vascular permeability by the Evans-blue test was also noted with all 4 agents, and zones were of comparable size after injection of the highest concentration of each agent.The results indicate thatin vivo, doxorubicin, daunorubicin, rubidazone and aclacinomycin A cause a rapid release of histamine from rat mast cells and an increase in vascular permeability in rat skin. There also appeared to be a reasonable correlation between the blueing reaction and histamine release in the peritoneal cavity in that the doses that did not cause skin blueing also failed to cause histamine release. The lack of histamine release by doxorubicin from mast cell preparationsin vitro suggests that alterations to the doxorubicin molecule or the presence of other critical substances may be necessary for this activity to commence.     

The effect of tartrazine on histamine release from rat peritoneal mast cells

The release of histamine from purified rat peritoneal mast cells induced by specific antigen (egg albumin), compound 48/80 and calcium ionophore A23187 was modified by tartrazine. Histamine release induced by 48/80 and antigen was inhibited by the presence of 10⁻⁵ to 10⁻²M tartrazine. The inhibitory effect on egg albumin induced histamine release was maximal when the tartrazine was added simultaneously with egg albumin, and was reduced by increased preincubation of the cells with tartrazine. Tartrazine had a small inhibitory effect on ionophore induced release at high concentrations, but augmented histamine release at tartrazine concentrations of 10⁻³ and 10⁻⁴M. Augmentation of ionophore induced release was maximal at between 0–5 min preincubation of the cells with tartrazine.     

The effect of captopril on histamine release from purified rat mast cells

OBJECTIVE: Captopril as inhibitor of angiotensin-converting enzyme is widely used in cardiovascular therapy, however, in some patients this drug causes allergic side effects. This fact suggests that captopril may release histamine from mast cells. MATERIALS AND METHODS: Peritoneal mast cells were obtained from rats. The cells were purified by Percoll. Aliquots of mast cells were incubated with captopril or with vehicle. Histamine was determined by the spectrofluorimetric assay. RESULTS: The results were analyzed with the Kruskall-Wallis (ANOVA) test. The study has shown that captopril releases histamine from mast cells. The process depends on Ca2+ presence in the incubation environment. Sodium cromoglycate, as mast cell membrane stabilizer, inhibits the effect of captopril. CONCLUSIONS: Our results suggest that allergic side effects of captopril may be linked to histamine release from mast cells.     

Inhibitory effect of traxanox sodium on IgE-mediated histamine release from passively-sensitized mast cells of the rat in vitro

Traxanox sodium, a benzopyranopyridine derivative showing a potent oral antiallergic activity in the rat, was compared with disodium cromoglycate (DSCG) for ability to block the release of histamine from the rat mast cell in vitro. Traxanox sodium showed dose-, antigen- and time-dependent inhibiton of the IgE-mediated release of histamine. The 50% inhibitory concentration was 0.04 microM for traxanox sodium, 1 microM for DSCG and 660 microM for theophylline. All these drugs blocked the release of histamine potentiated by preincubation of the mast cell with 10 micro M adenosine at lower concentrations than those which could inhibit the IgE-mediated histamine release. In addition, traxanox sodium at concentration of 1-100 microM inhibited the histamine release caused by 0.25 microgram/ml compound 48/80 in the presence and absence of calcium, and the drug at 100 micro M slightly inhibited the release caused by 0.2 microgram/ml ionophore A23187. These results suggest that traxanox sodium is a more potent inhibitor than DSCG on the histamine release from the mast cells of the rat, and a part of its antiallergic action is due to a selective inhibition of the immunological release of allergic mediators from the mast cell.     

Binding of dexamethasone and its effect on histamine release from rat mast cells

Purified rat peritoneal mast cells were incubated for 20 h with or without dexamethasone (4 x 10(-6) M) and then passively sensitized with serum from Trichinella spiralis-infected rats. The release of histamine using various secretagogues (concanavalin A, crude antigen of T. spiralis and polymyxin B) was determined. Dexamethasone treatment markedly inhibited IgE-dependent release of histamine (from 33.9 +/- 5.0% to 12.4 +/- 5.1% and from 39.8 +/- 7.9% to 14.2 +/- 6.5% of total cellular histamine content, respectively) whereas histamine release stimulated by the nonimmunological stimulus, polymyxin B was unaffected by this steroid. This suggests that the effects of dexamethasone cannot be exclusively explained by inhibition of phospholipases. Specific binding of 3H-dexamethasone to purified mast cells displayed sigmoidal dependence on concentration which may be the result of either negative cooperativity or the presence of a different class of binding sites. Two saturation plateaux at 20-30 x 10(-9) M and 70-90 x 10(-9) M were observed. The equilibrium dissociation constant for the higher affinity binding sites was Kd1 = 1.9 x 10(-8) M and represented 25,290 sites/cell, whereas the apparent Kd2 for lower affinity sites amounted to 5.5 x 10(-8) M and represented about 120,000 sites/cell.     

Inhibitory effect of the stereoisomers of dimethindene maleate (Fenistil®) on histamine release from rat peritoneal mast cells

Dimethindene maleate (DM) (Fenistil^R) is a potent antihistamine with a prolonged duration of action. In the present study, the racemic (±) form of DM and its individual (+) and (−) optical isomers were shown to be weak or non-releasers of histamine from rat peritoneal mast cells and to produce a comparable, dose-dependent inhibition of anti-IgE-induced histamine release from the same cell type. As such, the inhibitory activity of DM on the mast cell is probably due to the stabilization of this cell type rather than an interaction with the H₁-receptor.

     

Mechanism of histamine release from rat peritoneal mast cells

Summary The present communication endeavours to elucidate the mechanism of histamine release from rat peritoneal mast cells induced by selective histamine liberators.Of the different enzymatic processes involved in secretion the following are considered: ecto-ATPase activity in the mast cell, pro-esterase-esterase conversion during histamine secretion, cyclic AMP and microtubule association/dissociation, phospholipase A₂ and the effect of phospholipid metabolites on secretion, N-methyl transferase and the methylation of phospholipids and the phosphorylation and desphosphorylation of proteins.     

Juxtacellular histamine concentration governs histamine release from rat peritoneal mast cells

Isolated rat peritoneal mast cells release histamine when superfused with isoosmotic salt or sucrose solutions. The release was ascribed by us to an intracellular ion exchange between potassium and histamine at granule sites, resulting from a flux of cytoplasmic potassium across the granules secondary to the disturbance of the ‘state of equilibrium’ at the cell surface caused by the superfusion (Uvnäs et al. 1989). In the present article is shown that the histamine releasing effect is counteracted by the addition of histamine to the superfusion fluid. The inhibition is concentration-dependent and accompanied by concomitant changes in the potassium efflux. A 50% inhibition of the histamine release requires an external histamine concentration of 40 μm and extrapolation of the equilibrium curve hints at a total inhibition at concentrations around 170 μm. The observations are taken to indicate that reduction of the juxtacellular histamine concentration caused by the superfusion disturbs the histamine equilibrium at the mast cell surface resulting in the activation of the histamine secretory mechanism. In other words, the secretory activity of the mast cell is checked by the juxtacellular concentration of histamine. When the juxtacellular histamine is removed e.g. on isolation procedures, other experimental situations such as superfusion, or by consumption in vivo the mast cell delivers histamine to restore the juxtacellular equilibrium.     

Mitoxantrone induces nonimmunological histamine release from rat mast cells

The antineoplastic drug mitoxantrone (MTX) elicits a fast nocytotoxic and nonimmunological histamine release from peritoneal and pleural rat mast cells. The non specific phosphodiesterase inhibitor isobuthylmethylxantine (1 mM) decreases the potency of MTX. Theophylline (10 mM) decreases both the potency and the efficacy of MTX-induced histamine secretion. The protein kinase C (PKC) activator, tetradecanoyl-phorbol-13-acetate (50 ng/mL), enhances the effect of MTX, whereas the non specific PKC inhibitor trifluoperazine (10 M) exerts no effect.Histamine release was also unaffected by substances acting on G-proteins, namely pertussis toxin (200 ng/mL), cholera toxin (300 mg/mL) and benzalkonium chloride (10 g/mL). The inhibition of protein phosphatases 1 and 2A by okadaic acid (1 M) does not modify the response. The results indicate that mitoxantrone elicits the exocytosis in mast cells by a mechanism similar to the parent compound adriamycine, but different to the polyamine compound 48/80.accepted by W. Lorenz     

Effect of dantrolene on histamine release from rat peritoneal mast cells

Dantrolene strongly and dose-dependently inhibited histamine release from rat peritoneal mast cells induced by anti-IgE. Dantrolene inhibited Ca²⁺-mobilization from intracellular Ca²⁺-store as well as histamine release in mast cells activated by anti-IgE, the effect on both of these phenomena being closely correlated. These results suggested that the effect of dantrolene on histamine release from rat mast cell might be due to the inhibition of Ca²⁺-release from intracellular Ca²⁺-store.     

Influence of DPPE on histamine release from isolated rat mast cells

A second messenger function for histamine has been proposed based on the effects of the anti-estrogen drug DPPE (N,N-diethyl-2-(4-(phenylmethyl)phenoxy) ethanamine.HCl). The ability of DPPE to inhibit concanavalin A-induced histamine release led to the present investigation of its influence on the mast cell response to a wider selection of secretagogues. DPPE was an efficient inhibitor of antigen-induced release, while responses to compound 48/80 were virtually unaffected. Responses to the ionophore A23187 could be enhanced as well as inhibited, whereas the influence of DPPE on the combination of the ionophore and the phorbol ester TPA was variable and small. These results seem to exclude an involvement of a DPPE-sensitive histamine-mediated signal system of common importance in mast cell histamine release.     

Effect of staurosporine on histamine release from rat serosal mast cells

Rat serosal mast cells were challenged with compound 48/80 or calcium ionophore A23187 and the effect of staurosporine, a new inhibitor of protein kinase C, on histamine release from the cells was investigated. Histamine release induced by compound 48/80 or calcium ionophore A23187 was inhibited by staurosporine in a concentration-dependent manner and 0.1 and 1 microM staurosporine inhibited the histamine release significantly. The inhibitory effect of K-252a, another novel protein kinase C-inhibitor, was significantly higher than that of staurosporine on calcium ionophore A23187-induced histamine release. These results suggest that protein kinases will be involved in the process during mediator release from rat serosal mast cells.     

Failure of acetylcholine to release histamine from rat mast cells

The action of various salts of acetylcholine on isolated mast cells from Wistar and F₁ hybrids of Wistar and August rats was investigated.None of the acetylcholine salts within the concentration range 10^–12 M to 10^–2 M was able to release histamine either from Wistar or from hybrid mast cells. Compound 48/80, used as a control, was active in both cases.The results obtained are in opposition to some recent reports. The possible reasons for these contradictions are discussed.This work was supported by the Polish Academy of Sciences (Grant No. 10.5).     

Mechanisms of vancomycin-induced histamine release from rat peritoneal mast cells

The mechanisms of vancomycin (VCM)-induced histamine release were studied with rat peritoneal mast cells. VCM (>1×10^–3 M) released histamine from the isolated mast cells in a dose-dependent and noncytotoxic manner. In the absence of extracellular Ca²⁺, the histamine release was reduced markedly. When the intracellular Ca²⁺ was depleted, it was further decreased. The Fura-2-loaded single mast cells showed a biphasic increase in the intracellular Ca²⁺ concentration ([Ca²⁺]_i) by VCM: the first transient and the second sustained components. In the absence of extracellular Ca²⁺, the transient component was unchanged, while the sustained component was eliminated completely. The IP₃ content in the mast cells increased within 10 s after the application of VCM. These results suggest that VCM releases histamine from rat peritoneal mast cells via an IP₃ production and increase in [Ca²⁺]_i.     

Juxtacellular histamine concentration governs histamine release from rat peritoneal mast cells.

Isolated rat peritoneal mast cells release histamine when superfused with isoosmotic salt or sucrose solutions. The release was ascribed by us to an intracellular ion exchange between potassium and histamine at granule sites, resulting from a flux of cytoplasmic potassium across the granules secondary to the disturbance of the 'state of equilibrium' at the cell surface caused by the superfusion (Uvn?s et al. 1989). In the present article is shown that the histamine releasing effect is counteracted by the addition of histamine to the superfusion fluid. The inhibition is concentration-dependent and accompanied by concomitant changes in the potassium efflux. A 50% inhibition of the histamine release requires an external histamine concentration of 40 microM and extrapolation of the equilibrium curve hints at a total inhibition at concentrations around 170 microM. The observations are taken to indicate that reduction of the juxtacellular histamine concentration caused by the superfusion disturbs the histamine equilibrium at the mast cell surface resulting in the activation of the histamine secretory mechanism. In other words, the secretory activity of the mast cell is checked by the juxtacellular concentration of histamine. When the juxtacellular histamine is removed e.g. on isolation procedures, other experimental situations such as superfusion, or by consumption in vivo the mast cell delivers histamine to restore the juxtacellular equilibrium.