Histamine release from saponin-permeabilized rat mast cells by calcium

The first effect of receptor activation on the mast cell surface, initiating histamine secretion, is an increase in the cytosol Ca2+ concentration. It should then be possible to induce histamine secretion by calcium alone, if the calcium permeability of the cell membrane could be increased without any significant interference with the physiological cell functions. This was achieved in the present study by adding low concentrations of saponin (0.0005% and 0.001% w/v) to the medium. When calcium was added to the saponin-permeabilized cells, around 40% histamine release occurred with 0.25 mM extracellular calcium (free Ca2+ 0.15 mM). The release was inhibited by antimycin A (1 microM). Transmission electron microscopy showed formation of vacuoles containing granules stripped of their membranes, which characterize a secretory response. The observations are consistent with a limited increase in the calcium permeability of the cell membrane for a brief period. There was apparently an increase in the cytoplasmic calcium concentration, which acted through calmodulin, since the histamine release induced by calcium from the permeabilized mast cells could be inhibited by a calmodulin-antagonist, mepacrine (10-30 microM).     

Histamine release from rat mast cells induced by econazole.

1. Econazole released histamine from rat mast cells in vitro. This response was not affected by the addition of calcium or by prior treatment of mast cells with EDTA or cromoglycate. 2. Rat mast cells treated with econazole were stained by the vital dye trypan blue. 3. The intradermal injection of econazole increased vascular permeability. This response was antagonized by chlorpheniramine and cyproheptadine. 4. Our results demonstrate that econazole releases histamine by the "nonselective" mechanism. It is suggested that econazole inflammatory effects may be due to histamine release from mast cells.     

Histamine release induced by histone and phorbol ester from rat peritoneal mast cells

Histone 10 to 50 micrograms/ml released histamine from rat peritoneal mast cells in the absence of extracellular calcium. Extracellular calcium, 1 mM produced a slight shift of the histone dose-response curve to the right. In the absence of extracellular calcium, the histamine release-response to combined stimulation with histone and substance P was saturable. Neither histone nor substance P elicited any further response when one of these agonists alone was already eliciting a maximum response, although the cells were capable of a greater degree of histamine release in the presence of compound 48/80. In the presence of extracellular calcium, substance P at a concentration not by itself producing a response, acted synergistically with histone to induce histamine release. The substance P antagonist, SP-A, inhibited histamine release by histone. The phorbol ester, TPA, released histamine in a dose-dependent manner and this response was inhibited by SP-A. It is suggested that substance P and histone interact with a common site to release histamine and the role of protein kinase C in this release mechanism is discussed.     

Histamine release from rat mast cells induced by protamine sulfate and polyethylene imine

The protamine sulfate-induced release of histamine from mast cells in a non-cytotoxic reaction, similar to the 48/80-induced secretion. Polyethylene imine was found to be a less potent releaser. It is a cytotoxic substance without specificity for mast cells and acts on membranes generally. Although the two agents are related concerning their molecular weight and polybasicity, their mode of action on mast cells is clearly different.     

Histamine release induced from rat mast cells by the ionophore A23187 in the absence of extracellular calcium

Isolated rat mast cells were used to study whether ionophore A23187 could induce histamine release by mobilizing cellular calcium. The histamine release was a slow process which was completed after about 20 min incubation with A23187. The A23187-induced histamine release was inhibited after incubation of the cells with EDTA for 1 h in a 37°C water bath in calcium-free medium. Reintroduction of calcium in excess of EDTA induced the release of histamine. The observations suggest that A23187 can induce histamine release by mobilizing a cellular pool of calcium.     

Histamine release from rat peritoneal mast cells by kinin antagonists

Kinins are known to be potent releasers of histamine. In the present study, the B2 antagonist analogues of bradykinin (BK) and kallidin (KD): [( Thi6,9,D-Phe8]KD, [Thi5,8,D-Phe7]BK) were also found to be potent releasers of histamine from rat mast cells and not to exert any antagonistic effect. Similarly, two B1 receptor antagonists, des-Arg10-[Leu9]KD and des-Arg9-[Leu8]BK, were shown to promote histamine release and acted only as agonists. The order of potency of these analogues was the following: [Thi6,9,D-Phe8]KD greater than [Thi5,8,D-Phe7]BK greater than des-Arg10- [Leu9]KD greater than des-Arg9-[Leu8]BK. The high activity of some of these compounds suggests that (1) the potency of kinins for histamine release from rat mast cells not only increases in parallel with the number of positively charged amino acids (Lys, Arg) but also, because of others factors such as peptide conformation, receptor binding affinity or receptor accessibility, (2) the histamine release by kinins is either a non-specific effect not mediated by receptors or, if receptors are involved, these sites may be different from other kinin receptors (i.e. B1 or B2).     

Histamine release from rat neutrophils and mast cells as induced by ionophore--a pharmacological approach--.

A comparative study was carried out on the histamine release from rat neutrophils and mast cells by calcium ionohpore A 23 187 (Ionophore). A maximum release of histamine from neutrophils was induced by 10(-6) g/ml Ionophore and that from mast cells was 5 x 10(-6) g/ml. A fairly good correlation was found between the 45Ca incorporation into and the histamine release from both cells. The Ionophore-induced histamine release from both cells was decreased in Ca2+-free Tyrode's solution and by pretreatment with 0.05 M EDTA. Effects of different drugs on Ionophore-induced histamine release from neutrophils were similar to those seen in mast cells. Dibutyl cyclic adenosine monophosphate, theophylline, isoproterenol and prostaglandin E1 had not or only a slight inhibition on the release. The dose dependent inhibition of release was observed with disodium cromoglycate, N-(3',4'-dimethoxycinnamoyl) anthranilic acid and disodium baicalein phosphate, in experiments using both cells. Colchicine did not inhibit the reaction in these cells, however phosphatidylserine enhanced the reaction. On the other hand, the effect of concanavalin A was different in each type of cells, the release from mast cells was inhibited while the release from neutrophils was potentiated. These findings suggest the similarity of biochemical events in Ionophore-induced histamine release from neutrophils and mast cells.     

Histamine release from isolated and intact mast cells of two types of genetically different rat

A comparison has been made of the release of histamine from tissues of conventional rats, induced by injections of antigen, concanavalin A and clinical dextran, with that from rat isolated peritoneal mast cells. Concanavalin A was less active than dextran when injected into the skin or paws, but the reverse was found when the substances were tested on isolated cells. Similar results were obtained when a pure line of rats relatively resistant to dextran was used, concanavalin A being much more active on isolated cells than on intact mast cells. Antigen was equally active in the two types of rat. It is important, therefore, to state the experimental conditions when comparisons of the activities of histamine releasers are being made.     

Histamine release from human adenoidal and mesenteric mast cells induced by bacterial antigens

The histamine-releasing capability of Staphylococcus aureus antigens was examined in human adenoidal and mesenteric mast cells obtained by enzymic dispersion of tissues from non-allergic patients. Both populations of mast cells released histamine after challenge with bacterial protein in concentrations between 5-500 micrograms/ml. The release was dependent on the dose, temperature and metabolic energy. The maximum release was observed at 15 min after challenge. The present results suggest that Staphylococcus aureus antigens release histamine from human adenoidal and mesenteric mast cells via a non-cytotoxic, active secretory process.     

Histamine release from rat mast cells sensitized with mouse antiserum

The characteristics of the antigen-induced and non-antigen-induced histamine release from rat peritoneal mast cells sensitized in vitro with mouse anti-ovalbumin serum were investigated. The effects of some antiallergic drugs on these release reactions were also studied. Besides antigen-specific IgE antibody, heat-labile factor(s) responsible for the non-antigen-induced histamine release were found in mouse antiserum. Such factors were also present in normal mouse serum. In the absence of antigen, the combination of phosphatidyl serine and Ca++ induced some extent of histamine release from mast cells treated with these factors. From the present results it is suggested that quercetin selectively and verapamil primarily act to block calcium-gate opening resulting from antigen-antibody interaction on the mast cell membrane, while theophylline and disodium cromoglycate selectively inhibit the passage of calcium through open calcium channels.     

Histamine release induced by antimicrobial agents and effects of antimicrobial agents on vancomycin-induced histamine release from rat peritoneal mast cells

Vancomycin and certain fungicides may cause anaphylactoid reactions. We investigated the effects of vancomycin, miconazole and fluconazole on histamine release in rat peritoneal mast cells. Vancomycin and miconazole provoked histamine release in a dose-dependent manner. In contrast, fluconazole did not provoke histamine release at concentrations of 3 x 10(-6)-3 x 10(-3) M. Vancomycin is efficacious in the treatment of gram-positive bacterial infections; patients presenting themselves with mixed infections require concomitant therapy with a second antimicrobial agent. We investigated the effect of fosfomycin sodium, cilastatin sodium or fluconazole on vancomycin-induced histamine release. Fosfomycin sodium inhibited vancomycin-induced histamine release but neither cilastatin sodium nor fluconazole inhibited it in the mole ratios of daily doses used in humans. These results suggest that vancomycin and miconazole provoke histamine release in rat mast cells, but that fluconazole probably does not, while fosfomycin sodium may inhibit vancomycin-induced histamine release.     

Histamine release from rat mast cells induced by an extract from the sea urchin Toxopneustes pileolus

—The extract caused a dose-dependent release of histamine from rat peritoneal mast cells which was slower in onset than that of compound 48/80. It is also suggested that the extract-induced histamine release is dependent on aerobic glycolysis.     

Histamine release from canine lung and liver mast cells induced by radiographic contrast media

Radiographic contrast media are commonly used diagnostic aids to improve imaging, e.g. in computerized tomography. However, the routine application of these agents may cause adverse allergic/pseudoallergic reactions. In order to understand more completely the underlying mechanisms involved in these reactions, experiments on histamine release both in vivo and in vitro are necessary. Using canine mast cell suspensions from lung and liver, we have investigated the histamine release caused by six commonly used preparations. The dog is an ideal model for both in vitro and in vivo studies not only by virtue of its size but also because of its similarity to man with respect to e.g. cardiovascular reactions after drug-induced histamine release. The two non-ionic preparations (Solutrast, Ultravist) released little histamine from both cell types (ca. 4-6%). The ionic contrast media (Angiographin, Hexabrix, Telebrix, Rayvist) dose-dependently released histamine from the liver cells and pulmonary cells (maximum release between 18-35%). The liver cells (the liver is the shock organ in the dog) reacted more strongly to these agents than the pulmonary cells, thus providing further evidence for mast cell heterogeneity and the importance of selecting the appropriate mast cell model for the investigation.     

Histamine release from human pulmonary mast cells

The enzyme collagenase was used to disperse human lung into its component cells. The resulting cell suspensions contained circa 8% mast cells and were used for studies of mediator release without further purification. They exhibited a low (circa 7%) spontaneous release of histamine. They could be sensitized passively and released histamine upon challenge with anti-human IgE. They responded to concanavalin A but not to dextran. Phosphatidyl serine did not potentiate the release induced by these agents. The calcium ionophores, A23187 and ionomycin, both elicited histamine release. The cells were refractory to the action of the basic releasers 48/80 and peptide 401 (MCD-peptide). These results indicate marked differences between human pulmonary mast cells and the more widely used rat peritoneal mast cells.