Immunological Release Of Histamine Research Articles

Immunologic histamine release in vitro from the heart and lung of the cynomolgus monkey.

Immunologic histamine release was evoked from the sensitized fragmented cardiac and pulmonary tissue of the cynomolgus monkey by a reverse anaphylactic reaction. Ventricular and pulmonary tissue released a similar fraction (approximately 6%) of the total tissue histamine when challenged with antihuman IgE, presumably reflecting the 'active' sensitization of the monkey in vivo. Passive sensitization of these tissues in vitro resulted in significantly greater immunologic histamine release in 6 of the 14 ventricles and d a similar fraction (approximately 6%) of the total tissue histamine when challenged with antihuman IgE, presumably reflecting the 'active' sensitization of the monkey in vivo. Passive sensitization of these tissues in vitro resulted in significantly greater immunologic histamine release in 6 of the 14 ventricles and d a similar fraction (approximately 6%) of the total tissue histamine when challenged with antihuman IgE, presumably reflecting the 'active' sensitization of the monkey in vivo. Passive sensitization of these tissues in vitro resulted in significantly greater immunologic histamine release in 6 of the 14 ventricles and in the lungs. The antiallergic compounds, disodium cromoglycate and SK&F 64398, inhibited immunologic histamine release from passively sensitized monkey ventricular tissue. These results demonstrate that ventricular histamine may be immunologically released and that this release process can be pharmacologically inhibited in a manner similar to that of pulmonary tissue.

Effect of variation in endogenous levels of ascorbic acid on the in vitro immunological release of histamine and slow reacting substance of anaphylaxis from actively sensitized guinea-pig lung fragments.

1. The in vitro immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) from actively sensitized guinea-pig lung fragments was greatly reduced when the animals were maintained on an ascorbic acid-deficient diet. Excessive dietary levels of ascorbic acid did not increase mediator release above normal levels. 2. Restoration of ascorbic acid in the diet of scorbutic guinea-pigs restored in vitro immunological histamine to normal levels. 3. Variation in dietary levels of ascorbic acid had no effect on lung histamine content. 4. The lung ascorbic acid content was proportional to the dietary intake. Approximately 60% of the total lung ascorbic acid was removed by the process of chopping and washing of the tissue. This relationship was independent of dietary intake. 5. The results indicate that the immunological release of mediators of inflammation from guinea-pig lung is dependent on adequate endogenous levels of ascorbic acid.

Biological variation in the immunological release of histamine from replicates of passively sensitized human lung and its relation to histamine content.

The histamine content of weighed replicates of chopped human lung was found to vary greatly. Replicates also varied considerably in the amount of histamine released after passive sensitization with IgE and challenge with antigen. The amount of immunological release of histamine was poorly related to tissue histamine content. Consequently, expression of release as percent of content did not lead to any decrease in the amount of variation between replicates.

Effect of aspirin and indomethacin on the immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) from guinea-pig lung tissues (author's transl)

Effect of aspirin and indomethacin on the immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) from guinea-pig lung tissues (author's transl)

Stimulation of the antigen-induced contraction of guinea-pig trachea and immunological release of histamine and SRS-A from sensitized guinea-pig lung by (2-isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin.

1 (2-Isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin reduced basal tension and enhanced the antigen- and histamine-induced contractions of tracheal spirals obtained from actively sensitized guinea-pigs. The stimulating effect of L8027 required the presence of the drug, while that of indomethacin persisted after its removal from the organ bath. 2 L8027 and indomethacin stimulated the immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) and inhibited the de novo synthesis and release of malondialdehyde from actively sensitized guinea-pig lung fragments. 3 L8027 was 2,800 times more potent than indomethacin in both in vitro models of anaphylaxis. 4 A selective antagonist of SRS-A (FPL 55712) inhibited contractions produced by antigen, but had no effect on contractions produced by histamine. 5 Prostaglandins E and F2 alpha were continuously released into the organ bath fluid by the resting trachea. Contractions induced by antigen or histamine increased the rate of prostaglandin efflux. 6 L8027 had no effect on the efflux of prostaglandins E and F2 alpha at rest and during contraction. Indomethacin inhibited prostaglandin efflux at rest and during contraction while present in the organ bath. Prostaglandin efflux was restored to 80% of control after removal of indomethacin. 7 The results suggest that prostaglandins E and F2 alpha have no role in the stimulation by L8027 and indomethacin of the contractile responses of guinea-pig trachea. The possible mechanism for the effects of these drugs is discussed.

Effect of synthetic cyclic nucleotides on immunologic histamine release from calf granulocytes.

Sensitized bovine granulocytes release histamine when exposed to specific antigens. A unique modulation of histamine release by adrenergic agents has been shown in the bovine; beta-adrenergic agonists enhance and alpha-adrenergic agonists inhibit histamine release. This is an opposite response to that reported in other species. The present study was undertaken to determine the possible relationship between cyclic nucleotides and adrenergic agents in this species. Dibutyryl cAMP enhanced antigen-induced histamine release over the complete concentration range tested (10(-6)--10(-3)M); it also overcame, in a dose-dependent manner, the inhibition of antigen-induced histamine release produced by 10(-4) M phenylephrine. The 8-bromo cGMP AND 0-MONOBUTYRYL CGMP had no significant effect on antigen-induced histamine release nor did 8-bromo-cGMP have any significant effect on the enhancement of histamine release produced by 10(-4) M dibutyryl cAMP. These findings suggest that only cAMP has a role in the modulation of antigen-induced histamine release from bovine granulocytes.

Pharmacological basis of immediate hypersensitivity in the domestic fowl: a review

This review discusses the mechanisms of immediate hypersensitivity and their putative relationship to clinical syndromes in the fowl. The general features of these mechanisms are outlined, in terms of the pharmacological mediators involved, the anaphylactic antibodies, and the distribution and relative significance of the immune target cells — the mast cells and basophils. Emphasis is given to the ways in which these features are similar to or differ from those occurring in mammals. Consideration is given to the immunological release of histamine and of SRS‐A in the fowl. The results of work on the mechanisms of in vitro anaphylaxis (Schultz‐Dale phenomenon) in the chicken are discussed. The roles of several potential mediators of acute systemic anaphylaxis are discussed in some detail, with reference to the activities of antagonists to each of these potential mediators. A major role for the vasoactive lipids and peptides is suggested.

Immunological Release of Histamine from Human Lung

The experiments reported in this work have been performed to measure the effects of acetylcholine and the anticholinergic agent ipratropium bromide on the antigen-induced release of histamine from sensitized human lung in vitro. Primarily, ipratropium bromide did not have any effect, even at higher concentrations. Acetylcholine at a concentration of 1 x 10(-7)M increased the antigen-induced release of histamine by approximately 41%. When the lung tissue was treated with ipratropium bromide before acetylcholine, the competitive inhibition of the cholinergic receptor almost completely abolished this acetylcholine-induced increase of histamine release. Therefore, in our opinion, anticholinergic agents are primarily useful in vagus-controlled chronic obstructive ventilatory disorders; they are of secondary importance in allergic bronchial asthma.

Role of homocytotropic antibodies in pathogenesis of gastric ulcer.

Praomys (Mastomys) natalensis were sensitised by peritoneal injection of ovalbumin mixed with aluminium hydroxide. The animals developed homocytotoropic IgE and IgG 1 antibodies. When presensitised animals were challenged with ovalbumin in the gastric wall, a gastric ulcer appeared. This ulceration, induced by an immunological release of histamine, could be inhibited by the administration of disodium cromoglycate. The present model is useful for producing a gastric ulcer in a determined site. It supports the theory of a possible allergic component in the pathogenesis of the human disease.

Immunological release of histamine from human lung. I. Studies on the beta 2-sympathomimetic stimulator fenoterol.

Human lung tissue passively sensitized with anti-grass pollen IgE antibodies release histamine upon exposure to specific grass pollen antigen. Fenoterol, a beta 2-sympathomimetic stimulator drug, is shown to be a potent inhibitor of antigen-induced release of histamine. This inhibitory effect occurred with fenoterol concentrations of 2 x 10(-8) to 1 x 10(-7) M, and was determined by 67 and 95%, respectively. Thus, the beta 2-receptor stimulator fenoterol is a valuable drug for treating allergic bronchial asthma since it exhibits a combination of prophylactic and direct therapeutic properties.

The effects of the immunologic release of histamine upon human lung cyclic nucleotide levels and prostaglandin generation.

The effect of the antigen-induced, immunoglobulin (Ig)E-dependent release of mediators from human lung tissue was analyzed for coincident changes in the tissue levels of cyclic nucleotides. Simultaneously with the appearance of mediators, lung cyclic guanosine 3',5'-monophosphate (GMP) increased from 0.9+/-0.2 to 12.63+/-4.5 pmol/mg protein and cyclic AMP increased threefold from the initial levels of 5.1+/-1.4 pmol/mg protein. The release of histamine and prostaglandin (PG)F(2alpha), as well as the associated increases in cyclic nucleotides, peaked within 10 min of anaphylaxis. Antagonists of histamine's H-1 receptor prevented anaphylaxis-associated increases in cyclic GMP, whereas H-2 antagonists prevented the cyclic AMP response. Neither of these antagonists influenced the pattern or quantity of histamine or slow-reacting substance of anaphylaxis release. Prevention of PGF(2alpha) synthesis with acetylsalicylic acid failed to influence histamine or slow-reacting substance of anaphylaxis release or the concomitant increases in cyclic nucleotides. Histamine, added exogenously, produced a prompt increase in the cyclic AMP and cyclic GMP levels of human lung. As was seen after anaphylaxis, H-1 anatagonists prevented the cyclic GMP response to histamine, whereas H-2 antagonists prevented the cyclic AMP response.H-1 antagonists prevented 50% of the PGF(2alpha) synthesis accompanying anaphylaxis; H-2 antagonists had no effect. Exogenous histamine induced PGF(2alpha) synthesis; this synthesis was prevented by H-1 but not H-2 antagonists, and was reproduced by 2-methylhistamine (H-1 agonist) but not by dimaprit (H-2 agonist). Arachidonic acid generation of PGF(2alpha) was not influenced by antihistamines. Therefore, histamine interactions with human lung result in the synthesis of both PGF(2alpha) and cyclic GMP in response to H-1 stimulation, and of cyclic AMP through H-2 stimulation.

Effect of disodium cromoglycate and Picrorhiza kurroa root powder on sensitivity of guinea pigs to histamine and sympathomimetic amines.

Four weeks pretreatment with disodium cromoglycate (DSCG) and the powdered roots of the herb Picrorhiza kurroa, Benth, rendered guinea pigs less sensitive to histamine when compared with appropriate controls. The bronchodilator effects of isoprenaline and adrenaline were found to be markedly enhanced. The severity and duration of the allergic bronchospasm was significantly less in animals pretreated with the two drugs. Furthermore, the total histamine content of the lung tissue in animals pretreated with DSCG and P. kurroa was significantly less than that in the untreated controls. The pretreatment was also found to exhibit inhibitory effect on the immunological release of histamine and SRS-A from chopped lungs.

Inhibition of antigen-induced histamine release by ouabain

The effect of ouabain, a specific sodium-potassium dependent adenosine triphosphatase (Na +-K +-ATPase) inhibitor, on antigen-induced histamine release was studied using guinea pig lung fragments sensitized in vitro with rabbit antibodies against bovine serum albumin. Histamine was assayed spectrafluorometrically. When sensitized tissue had been preincubated with ouabain (≤ 1.0 × 10 −4 M) for 10 min prior to antigenic challenge, release of histamine was significantly inhibited (maximum 54%, p < 0.001, N = 9, paired t test). The most significant inhibition was obtained, near the optimal concentration of antigen. The inhibition was dependent on the length of preincubation (≤ 20 min), and was partially reversible upon washing the tissue removing the ouabain. Ouabain did not seem to prolong the duration of the histamine release process. Increase in potassium ion (≤ 1.1 × 10 −2 M) inhibited the histamine release and had additive effects to ouabain action. Dibutyryl cyclic AMP (≤ 5 × 10 −3 M), which could enhance the release, strongly antagonized the inhibition. Glucose removal from the medium did not abolish the ouabain effect. The results seem to indicate that immunologic release of histamine is under the influence of the membrane Na +-K +-ATPase activity.

Immunological Release of Histamine and Slow Reacting Substance of Anaphylaxis (SRS-A) from Guinea-pig Lung

Immunological Release of Histamine and Slow Reacting Substance of Anaphylaxis (SRS-A) from Guinea-pig Lung

Immunological Release of Histamine and Slow Reacting Substance of Anaphylaxis (SAS-A) from Guinea-pig Lung

Immunological Release of Histamine and Slow Reacting Substance of Anaphylaxis (SAS-A) from Guinea-pig Lung

Dissociation of the Immunologic Release of Histamine and Slow Reacting Substance of Anaphylaxis from Human Lung Using Cytochalasins A and B

Abstract Cytochalasins A and B at low doses resulted in enhancement of the antigen-induced and anti-IgE-mediated release of histamine from human lung fragments in vitro. Both compounds appeared to effect a dose-dependent inhibition of the antigen-induced release of slow reacting substance of anaphylaxis. Although the effects observed with cytochalasin B were at least partially reversible, the effects of cytochalasin A could not be readily reversed. The cytochalasins appeared to be more effective when present during the antigen-dependent activation phase of mediator release rather than during the calcium-dependent release phase.

Effect of a histamine H-2-receptor antagonist on immunologically induced mediator release in vitro.

The histamine H2-receptor has been implicated in the autoregulation of endogenous histamine release from actively sensitized human basophils. Consequently, the activity of metiamide (SK & F 92058), a specific histamine H2-receptor antagonist, was investigated for its effect on immunologically-induced histamine release in several in vitro models of immediate hypersensitivity. Metiamide enhanced the release of histamine from passively sensitized fragmented Rhesus monkey lung and skin when these tissues were challenged in a reversed type anaphylactic reaction with antihuman IgE. The enhancing effect of metiamide on the release of ‘slow reacting substance of anaphylaxis, from monkey lung was considerably less pronounced. In contrast, metiamide failed to significantly enhance the antigen-induced release of histamine from fragmented rat lung which had been passively sensitized with rat anti-ovalbumin serum. The data supports a species-specific enhancement of immunologic histamine release in vitro, perhaps by H2-receptor blockade on cells responsible for such release.

On the immunological histamine release from guinea-pig lung and its inhibition by isoprenaline.

Abstract: Some experimental conditions in connection with the ovalbumin‐stimulated release of histamine from the actively sensitized guinea‐pig lung in vitro and the influence of isoprenaline on this release have been studied. At 37° the release process was completed within 15 minutes. Incubation did not change the tissue content of histamine extractable by boiling. Isoprenaline, 2×10‐8 M, inhibited 50–60 per cent of the control release of histamine. The effect was fully blocked by propranolol, 10‐7 M. The inhibitory effect of isoprenaline was found to be restricted to the calcium‐dependent release of histamine. The preincubation time of isoprenaline was not critical. An increase in the dose of antigen did not impair the ability of isoprenaline to inhibit the release of histamine.

Anaphylaxis in the guinea-pig isolated heart: selective inhibition by burimamide of the positive inotropic and chronotropic effects of released histamine.

1. Anaphylaxis was induced in the isolated heart of the guinea-pig in the presence of burimamide at concentrations of 4 x 10(-5)M and 2.7 x 10(-4)M.2. Burimamide did not affect the immunological release of histamine; however, it selectively antagonized the positive inotropic and chronotropic effects of released histamine. The antagonism of the positive chronotropic effect was concentration-dependent.3. Neither the negative dromotropic effect nor the decrease in coronary flow rate occurring during anaphylaxis were inhibited by burimamide.4. The results are in agreement with the double histamine receptor theory and suggest that, in the heart of the guinea-pig, H(2)-receptors are involved in the positive inotropic and chronotropic effects of released histamine, and H(1)-receptors in the negative dromotropic effect.

Immunologic Release of Histamine and Slow Reacting Substance of Anaphylaxis from Human Lung

Abstract The capacity of prostaglandins to suppress the IgE-dependent antigen-induced release of histamine from human lung tissue requires concentrations which increase tissue levels of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) and involves a receptor distinct from that utilized by beta adrenergic agents. The inhibition of histamine release and concomitant rise of cyclic AMP in response to prostaglandin E1 (PGE1) occurs in a dose response fashion, reaching a peak within 1 min and persisting for at least 60 min. That the supression of mediator release from the subpopulation of target cells by the prostaglandins is related to elevations in total tissue cyclic AMP is supported by the kinetic relationship of the two events, the augmentation of both events in the presence of a methylxanthine, and the finding that the relative potency of isoproterenol, norepinephrine, PGE1 and prostaglandin F2α (PGF2α) to inhibit mediator release is in accord with their relative capacity to elevate cyclic AMP. The finding that low doses of prostaglandins enhance mediator release while reducing tissue levels of cyclic AMP reveals that these agents could profoundly modulate the immunologic release of chemical mediators.