Anaphylactic Histamine Release Research Articles

Anaphylactic Release of Histamine and Slow Reacting Substance of Anaphylaxis (SRS-A) from Guinea-Pig Lung and its Modulation by Prostaglandins

The regulatory mechanism of anaphylactic release of histamine and SRS-A from passively sensitized guinea-pig lung tissue was studied. The release of histamine and SRS-A from sensitized lung tissue was markedly decreased by preincubating with isoproterenol, aminophylline, cyclic AMP•Na and PG E2. While the release of both chemical mediators was increased by preincubating with cyclic GMP•Na and PG F2 alpha, and by preincubating with the mixture of PG E2 and PG F2 alpha (1:9) the release of both chemical mediators was markedly increased comparing with that by preincubating with PG F2 alpha alone.

Release of mediators of anaphylaxis: inhibition of prostaglandin synthesis and the modification of release of slow reacting substance of anaphylaxis and histamine.

1 When isolated perfused lungs from sensitized guinea-pigs were challenged with antigen, histamine, slow reacting substance of anaphylaxis (SRS-A) and prostaglandin-like substances were released into the effluent. 2 Treatment of the lungs before and during challenge with indomethacin (0.5--10 microgram/ml), sodium aspirin (1--10 microgram/ml), sodium meclofenamate (0.1--1 microgram/ml) or ketoprofen (0.5--5 microgram/ml) inhibited the release of prostaglandins while increasing the output of histamine and SRS-A between three- and five-fold. 3 Diethylcarbamazine (0.2--1 mg/ml) reduced the release of SRS-A and histamine but increased the amount of prostaglandin-like substances produced. 4 Eicosatetraynoic acid (10 microgram/ml) inhibited formation of prostaglandins but did not modify release of histamine and SRS-A. 5 The results with non-steroid anti-inflammatory drugs and diethylcarbamazine suggest that prostaglandins, or some other product of the cyclo-oxygenase system, depress the anaphylactic release of SRS-A and histamine.

Histamine release from rat mast cells induced by Sendai virus.

SENDAI virus (HVJ, haemagglutinating virus of Japan), a type 1 parainfluenza myxovirus, agglutinates certain types of cells and induces cell fusion1. Previously2 we reported on the degranulating activity in the hybrid cells derived from rat mast cells and Ehrlich ascites tumour cells using HVJ. During that work, it was found that histamine release accompanied by degranulation from unfused mast cells occurred frequently. This observation led to the theory that histamine release from mast cells was induced by virus, as well as by antigen from sensitised mast cells and by histamine releasers. The results reported here indicate that histamine release from mast cells was induced by direct exposure of cells to virus in the presence of Ca2+ at 37 °C and that it was markedly enhanced by the addition of phosphatidylserine (PS), which is a selective enhancer3 of anaphylactic histamine release.

Further studies on the tachyphylaxis to DSCG. The effects of concentration and temperature.

The tachyphylaxis to DSCG's inhibition of anaphylactic histamine release has been demonstrated in passively sensitized rat lung fragments. The induction of tachyphylaxis appears to depend on the concentration of the drug and the length of pretreatment. Tachyphylaxis is relatively independent of the concentration of the second exposure to DSCG. The development of tachyphylaxis is highly temperature dependent; it can be prevented by cooling the tissues to 2-4 degrees C after a brief (30 sec) preincubation with DSCG. It is suggested that DSCG inhibits histamine release by binding to 'receptor' site(s). Once the site is occupied by DSCG, it is modified by a temperature-dependent process, thus losing the ability as a 'receptor' for inhibition of histamine release. The tachyphylaxis is the result of such a modification.

Inhibition of anaphylactic histamine release by Forssman antiserum. II. Mechanism of inhibition.

The mechanism was studied of the inhibitory effect of IgG Forssman antibody on anaphylactic sensitization in the guinea pig lung. Two possibilities were considered to explain the inhibitory effect: either the Forssman antibody-antigen interaction occurred on the mast cell, allowing the F(ab′)<sub>2</sub> portion to interfere with the Fc receptor(s) for anaphylactic antibody; or the interaction took place adjacent to the mast cell allowing the Fc portion to occupy the receptors for anaphylactic antibody. These studies were made possible in part by developing a method for preparing mast cell suspensions from guinea pig lung. The mast cells were viable but released histamine only on treatment with compound 48/80 and not with anaphylatoxin, soluble immune complexes or with active or passive anaphylactic sensitization. Mast cells incubated with Forssman antibody and complement showed no evidence of injury as judged by electron microscopy, suggesting that they did not contain Forssman antigen. The absence of Forssman antigen from mast cells was substantiated further by studies of mixed agglutination and fluorescence microscopy. Also, pepsin digestion of Forssman antibody resulted in a loss of the ability to inhibit the histamine-releasing activity of soluble immune complexes, indicating that the F(ab′)<sub>2</sub> portion alone was not sufficient to sustain the inhibitory process. It was concluded that the inhibitory effect of IgG Forssman antibody was due to union with interstitial Forssman antigen adjacent to mast cells, allowing the Fc portion of the Forssman antibody to irreversibly occupy the mast cell Fc receptor(s) for anaphylactic antibody.

Inhibition by 5-hydroxytryptamine of anaphylactic histamine release from bovine granulocytes

A suspension of granulocytes from calves sensitised to horse plasma released histamine when exposed to the antigen. Histamine release was strongly inhibited by 5-hydroxytryptamine in a dose-related fashion. 5-HT is known to be released from bovine lungs in vitro, and may regulate the release of histamine in vivo during anaphylaxis.

Potentiation of anaphylactic histamine release from isolated rat pleural mast cells by rat serum phospholipids.

Isolation of sensitized rat mast cells by density gradient centrifugation in Ficoll decreases the histamine release obtained when they are subsequently exposed to antigen. The histamine release from such isolated cells is potentiated by the addition of 2% boiled rat serum. This potentiation is dose-dependent and has a temperature optimum of about 25 degrees C. The potentiating activity was localized to the serum phospholipid fraction. Of the pure phospholipids studies (LPC, PC, PE, PI, PS and SM) only phosphatidylserine and lysophosphatidylcholine were found to potentiate the histamine release. The mechanism behind this potentiation is discussed and it is suggested that the potentiation by phosphatidylserine and lysophosphatidylcholine is due to a requirement of these phospholipids for the ion exchange (Na+, K+ and Ca++) or the adenylcyclase activity essential for the histamine release process.

Glycogenolysis and control of anaphylactic histamine release by cyclic adenosine monophosphate-related agents: I. Role of glycogen and glucose

The relationship of glycogen and glucose to anaphylactic histamine release from chopped sensitized guinea pig lung in vitro was studied. A parallelism was observed between the total amount of glycogen in the sensitized lung and the total amount of histamine released from the lung by antigen-antibody reactions. Removal of glucose from the medium for tissue suspension resulted in reduction in histamine release. Depletion of glycogen and/or glucose from the system was associated with (1) abolition of the inhibition of histamine release by isoproterenol and high concentrations of dibutyryl cyclic adenosine monophosphate (AMP) and (2) increase in the rate of enhancement of histamine release by lower concentrations of dibutyryl cyclic AMP. The results indicate that (1) glycogen may be one of the ultimate energy sources for anaphylactic histamine release, and (2) the presence of adequate amounts of glycogen and/or glucose in the sensitized tissue is necessary for the normal beta adrenergic effects on the histamine release in vitro from sensitized lung fragments.

Glycogenolysis and control of anaphylactic histamine release by cyclic adenosine monophosphate-related agents: II. Modification of histamine release by glycogenolytic metabolites

d-glucose-6-phosphate (⩽ 5 × 10 −3 M), pyruvate, lactate (⩽ 1 × 10 −2 M), and dibutyryl cyclic AMP (⩽ 5 × 10 −3 M) were capable of inhibiting anaphylactic histamine release in vitro from chopped guinea pig lung. In lower concentrations, pyruvic acid and lactate, as well as dibutyryl cyclic AMP, enhanced the release. Significant synergism was observed between pyruvate (5 × 10 −3 M) and isoproterenol (1 × 10 −8 M) in the inhibition of histamine release. The inhibitory actions of isoproterenol, glucose-6-phosphate, and pyruvate were influenced by calcium ion concentration. However, beta blockade, which diminished the isoproterenol effect, was without effect on pyruvate (1 × 10 −2 M) or glucose-6-phosphate (5 × 10 −3 M) action. Reduction of histamine release as the result of blockade of glycolysis by 2-deoxy- d-glucose was slightly but reproducibly reversed by the addition of pyruvate (1 × 10 −2 M) to the release system. Glucose-6-phosphate and isoproterenol did not have this effect. The results, together with a previous study, suggest that glycogenolysis may possess a role in the anaphylactic histamine release in vitro from sensitized lung fragments.

Ammonium and sulfate ion release of histamine from lung fragments.

In vitro studies with guinea pig lung fragments incubated with 10- to 200-mM concentrations of ammonium ion demonstrated the release of substanial quantities of histamine. Of the anions tested with ammonium ion, sulfate was the most potent, while nitrate and acetate ions were of intermediate potency and chloride was less potent. An osmotic effect is unlikely since equal concentrations of sodium chloride failed to release histamine. Isoproterenol, known to decrease anaphylactic histamine release, and acetycholine, known to increase histamine release, had no effect on the ammonium sulfate-mediated release of histamine. N-6 2'-O-Dibutyryladenosine 3',5' monophosphate (dibutyryl c-AMP) was also ineffective. These studies suggest that the inhalation irritation associated with certain sulfate and other salts, may be a function of their ability to release histamine in the presence of amonium ion.

Drug inhibition of anaphylactic histamine release from peritoneal cells of rats infected with Toxocara canis.

An experimental model for studying anaphylactic histamine release from rat peritoneal cells in vitro is described. Rats were sensitized by feeding the infective eggs of ttoxocara canis, the antigen being prepared from the infective eggs. The characteristics of histamine release are comparable with those found for other anaphylactic systems. Addition of 0.2% inactivated normal rat serum to the incubation media reduced the spontaneous histamine release from 11.5 +/- 1.9% to 3.1 +/- 1.6% (mean +/- SD) of total histamine, whereas the corresponding figure for anaphylactic histamine release was 41.3 +/- 19.7%. Both disodium cromoglycate (DSCG) and levamisole produced a dose-related inhibition of histamine release, with DSCG being the more potent drug.

Inhibition by derivatives of phloretin of anaphylactic histamine release from human lung tissue and of prostaglandin F2alpha-induced bronchoconstriction.

Derivatives of phloretin (25-1,000 mug/ml) among them polyphloretin phosphate (PPP), inhibited in a dose-dependent manner anaphylactic (birch pollen or horse dander) histamine release from human lung tissue passively sensitized with reaginic serum. Pretreatment with PPP of lung tissue sensitized both to birch pollen and horse dander counteracted to a similar extent the release of histamine induced by either allergen administered in sequence. The phloretin derivatives also antagonized the constrictor action of prostaglandin F2alpha on isolated human bronchi at concentrations which did not impair the responses to histamine. The low and high molecular weight derivatives of phloretin were comparably active on a weight basis in both experimental systems.

Studies on the role of calcium in the anaphylactic histamine release from isolated rat mast cells.

The anaphylactic histamine release from isolated, sensitized rat mast cells was studied. Before incubation the mast cells were kept concentrated (106 cells/ml) in either calcium‐free buffer (these cells are denoted Mc) or buffer containing 1 mM‐CaCl2 (denoted McCa). The cells were diluted 100 to 400 times when exposed to antigen. The histamine release from Mc and McCa exposed to antigen plus CaCl, was identical, but significantly lower than observed for McCa incubated with antigen alone. EDTA (1 mM) abolished the effect of CaCl2 in the incubation medium. Pre‐incubation of McCa in the absence of calcium decreased the response to antigen, and optimal reduction of histamine release was observed within one minute at 37° and five minutes at 21°. The time courses for the anaphylactic histamine release in the presence of calcium from Mc and McCa were identical at both 21° and 37°. The release from McCa in the absence of calcium was considerably faster at both temperatures.

Studies on the influence of calcium in the anaphylactic histamine release from isolated rat mast cells.

Studies on the influence of calcium in the anaphylactic histamine release from isolated rat mast cells.

Cyclic AMP, ATP, and Reversed Anaphylactic Histamine Release from Rat Mast Cells

Abstract Reversed anaphylactic histamine release by rabbit (Rab) anti-Rat Fab was independent of serum factors and was established as being noncytolytic in that challenged isolated mast cells still retained incorporated 42K and excluded trypan blue dye after releasing histamine. The release reaction involved the activation of a diisopropyl fluorophosphate (DFP)-sensitive esterase and required energy utilization. Prostaglandin E1 (PGE1) consistently produced a dose-related increase in the mast cell content of cyclic 3′,5′-adenosine monophosphate (cyclic AMP) which at the optimal concentration was 2 to 3 times the average baseline of 4.71 pmoles/106 mast cells (range -1 to 10 pmoles/106 mast cells). Aminophylline and PGE1 alone each inhibited Rab anti-Rat Fab-induced histamine release with concomitant increases in cyclic AMP, and the combination of these agents had a synergistic effect on both parameters. The inhibition of histamine release by the endogenous accumulation of cyclic AMP was reproduced by the exogenous administration of dibutyryl cyclic AMP. The interaction of Rab anti-Rat Fab with isolated mast cells resulted in a depletion of the cellular levels of cyclic AMP, ATP, and calcium in association with histamine release. Although these consequences of membrane perturbation may be unrelated, it seems more likely that they are interrelated and intrinsic to reversed anaphylactic histamine release.

Correlation between <i>in vitro</i> Anaphylactic Histamine Release from Tissues and Reagin Titer in Rat

The magnitude of antigen-induced histamine release from actively sensitized rat tissues <i>in vitro</i> was compared with the amount of specific reagin in the serum. There was no quantitative correlation between either, suggesting that the antigen-induced histamine release from sensitized tissues might depend on the ability of sensitized target cells to release histamine. In addition, the magnitude of antigen-induced histamine release was different in each tissue of sensitized rats. This also suggested that there might be some differences in the ability of sensitized target cells in each tissue to release histamine by antigen.

Liver histamine and zinc in guinea pig anaphylaxis.

The anaphylactic histamine release from guinea pig liver under amino-guanidine protection was studied <i>in vivo </i>by injecting antigen into the portal vein. No significant decrease of liver histamine could be observed 2 min after antigen, whereas a significant, though small increase of plasma histamine in the liver blood occurred indicating a histamine release of 1.2% of total liver histamine. When histamine was injected into the portal vein of normal guinea pigs at a dosage about 1.75 times the amount of total liver histamine, 48.8% or even more was retained by the liver. Since, on the basis of our previous studies on heparin release, the liver mast cell disintegration must be considered greater than is suggested by the extent of histamine output, much of the histamine released from the mast cells is probably taken up by the liver cells and metabolized. Zinc which is assumed to link histamine to heparin, was not increased in the liver blood plasma upon challenge with antigen. The guinea pig liver possibly acts as a buffer organ preventing histamine overload of the blood during anaphylaxis. It serves this function by binding hepatic as well as extrahepatic histamine, and in addition, by the heparin-mediated release and activation of liver histaminase which acts both locally and systemically.

Effect of divalent cations and metabolic energy on the anaphylactic histamine release from rat peritoneal mast cells.

Histamine release induced by the antigen from mast cells obtained from actively sensitized rats was enhanced by the same concentration of calcium in the medium, irrespective of whether the mast cells were isolated from contaminating cells or not. The time course of the release from isolated mast cells in the presence or absence of calcium was similar at 21 and 37 °C, respectively. The enhancing effect of calcium on the release was gradually lost when the cells were exposed to antigen prior to the addition of calcium. At equivalent concentrations, no other divalent cation tested could substitute for calcium. Similar concentrations of antimycin A prevented histamine release induced by antigen or compound 48/80. In the presence of the inhibitor, energy derived from glycolysis completely restored the release when induced by compound 48/80, whereas only partial restoration could be obtained in anaphylaxis. The latter effect was inhibited with iodoacetate in concentrations which were without effect in the absence of antimycin A. The results agree well with the view that antigen causes a passing state of increased permeability of the plasma membrane of the mast cells whereby calcium and eventually sodium might enter. Provided metabolic ATP is available, intracellular reactions are hereby initiated which lead to the release of histamine from its binding sites within the granular matrix.

Inhibition by cromoglycate of histamine release from rat peritoneal mast cells induced by mixtures of dextran, phosphatidyl serine and calcium ions.

1 Dextran releases histamine from rat peritoneal mast cells in the presence but not in the absence of phosphatidyl serine (PS). With PS (10 mug/ml) present the effect of dextran was concentration-dependent in the range of 0.2-6 mg/ml.2 PS releases little histamine on its own but mixed with dextran (6 mg/ml) produces a graded effect in the range of 0.3-10 mug/ml.3 The combination of dextran and PS releases no histamine in a medium containing less than 0.1 mM calcium. As the calcium concentration is increased, release occurs and a maximum is reached at calcium 1 mM; at higher concentrations release falls off sharply.4 Histamine release by the combination of dextran (6 mg/ml), PS (10 mug/ml) and calcium (1.8 mM) is inhibited by cromoglycate in the same range (1-30 muM) that inhibits anaphylactic histamine release from rat peritoneal cells.5 Inhibition by cromoglycate occurred with all dextran concentrations tested (0.2-15 mg/ml) but high concentrations of PS (30 and 100 mug/ml) overcame the effect of cromoglycate (2 and 10 muM). Calcium concentrations above 1 mM augmented inhibition by cromoglycate 2 and 10 muM.

Studies on the role of c-AMP in the regulation of the anaphylactic histamine release from guinea pig lung

Studies on the role of c-AMP in the regulation of the anaphylactic histamine release from guinea pig lung