Concanavalin A-induced Histamine Release Research Articles

Antiinflammatory Activity of Heat-treated <i>Cassia alata</i> Leaf Extract and Its Flavonoid Glycoside

Antiinflammatory activities of heat-treated Cassia alata leaf extract and kaempferol 3-O-gentiobioside (K3G) isolated from C. alata as an abundant flavonoid glycoside were studied by comparing their activities with the activities of sun-dried C. alata leaf extract. We observed strong inhibitory effects on Concanavalin A-induced histamine release from rat peritoneal exudate cells both in the extracts of heat-treated and sun-dried C. alata leaves. Furthermore, the heat-treated leaf extract exhibited stronger inhibitory effects than the effects of the sun-dried leaf extract at low concentrations in the studies of Concanavalin A-induced histamine release, 5-lipoxygenase inhibition, and also inhibition of cyclooxygenases (COX-1 and COX-2), whereas K3G showed weak inhibitory effects on Concanavalin A-induced histamine release, 5-lipoxygenase, and COX-1. No anti-hyaluronidase effect was detected in any of the materials tested.

Histamine release from cord blood basophils is influenced by plasma IgE concentration, osmolarity, gestational age at birth and atopic disposition

To characterize the normal values of histamine release from basophil leucocytes in cord blood after stimulation with both IgE-mediating and non-IgE-mediating secretagogues, a population of 1,684 newborn infants was studied using a microfiber-based method for detecting histamine release. A wide variation in anti-IgE and Concanavalin A-induced histamine release in the population was found. An increase in osmolarity in the release media selectively enhanced the maximal IgE-mediated histamine release, in addition to an increase in sensitivity in the dose response for anti-IgE and Concanavalin A. Both anti-IgE and Concanavalin A mediated histamine release were found to be significantly associated with the concentration of IgE in cord blood. Furthermore, an increased sensitivity to the IgE-mediated response and a close correlation between anti-IgE and Concanavalin A histamine release were found in the group of newborns with high IgE levels. Gestational age at birth and histamine release after stimulation with both IgE-mediating, and non-IgE mediating secretagogues were found to be significantly related, thus suggesting a continuing maturation of the human basophil leucocytes in the last weeks of gestation. Parental atopic disposition also affected basophil releasability in cord blood.

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.

Comparison of histamine release in cord blood and adult blood

Histamine release (HR) after stimulation with anti-IgE, concanavalin A (ConA) and Formyl-Met-Leu-Phe (FMLP) from 97 cord blood samples was compared to results obtained in identically treated blood samples from adults. The maximal HR obtained with anti-IgE did not differ significantly from the values obtained in adult blood, although a ten times higher concentration of anti-IgE was required for maximum release. Passive sensitization with IgE-rich plasma caused a significant increase in maximal anti-IgE-induced HR in the majority of cord blood samples, and the dose-response curve was similar to that obtained in adult blood. Challenge with ConA and FMLP caused a HR similar to that seen in adult blood, but the close correlation between anti-IgE- and concanavalin A-induced HR seen in adult blood was absent in cord blood.

Effect of the carboxylic ionophore monensin on histamine release from rat peritoneal mast cells

The effect of the monovalent carboxylic ionophore monensin, which mediates a one-for-one exchange of intracellular H+ for extracellular Na+, was investigated in purified rat peritoneal mast cells. Monensin inhibited histamine secretion induced by compound 48/80, adriamycin and the calcium ionophore A23187; the inhibitory effect was maximal when the compound was added at least 10 min before the secretagogues. Washing of cells before addition of the secretagogues did not abolish the inhibitory effect of monensin. On the contrary the carboxylic ionophore was completely ineffective in preventing concanavalin A-induced histamine release. When rat peritoneal mast cells were incubated in the presence of monensin for longer period (up to 5 hours), the substance induced a slow, progressive and dose dependent histamine release, which, at least for lower doses was noncytotoxic. The secretory effect of monensin was still present if the ionophore was washed away after 10 min of incubation, and the incubation continued in drug-free medium. Monensin stimulated histamine secretion was strictly dependent on extracellular Na+ concentrations, and independent on extracellular Ca++.

Synthetic retinoids inhibit histamine release from isolated human mast cells

In view of the immunomodulating properties of the synthetic retinoids etretinate and isotretinoin, their effects on isolated human mast cells were investigated. At concentrations of 10(-6) to 10(-5) M, isotretinoin and at 10(-6) M to 5 X 10(-5) M, etretinate inhibited concanavalin-A induced histamine release dose-dependently. Effective concentrations corresponded to achievable levels under therapeutic conditions in man. Without any additional stimulant, both drugs exhibited no appreciable effects with the exception of a toxic damage at very high levels.

Inhibition by calcium antagonists of histamine release and calcium influx of rat mast cells: Difference between induction of histamine release by concanavalin A and compound 48/80

The relation between calcium influx and histamine release from rat mast cells was investigated. When purified mast cells pretreated with a calcium antagonist (MnCl 2 or methoxyverapamil (D-600)) were exposed to concanavalin A or compound 48/80 in Tyrode solution (pH 7.4) at 37°C, the calcium antagonists inhibited the extracellular calcium-dependent component of concanavalin A-induced histamine release. MnCl 2 also inhibited the extracellular calcium-dependent component of compound 48/80-induced histamine release, whereas D-600 did not inhibit the release. D-600 inhibited the 45Ca uptake induced by concanavalin A, but did not inhibit the 45Ca uptake induced by compound 48/80. It was found that the inhibitory action of calcium antagonists depended on the uptake of extracellular calcium. These observations suggest that concanavalin A and compound 48/80 stimulate different mechanisms of calcium influx. Studies on inactivation of the mechanisms of calcium influx showed that calcium influx into cells activated by concavalin A stopped when concanavalin A was washed out, whereas the influxactivated by compound 48/80 was still operative after compound 48/80 had been washed out.

Characterization of augmentation of allergic and non-allergic histamine release by non-steroidal anti-inflammatory/analgesic agents.

Augmentation of allergic histamine release from human leukocytes previously was shown to be produced by numerous acidic anti-inflammatory/analgesic agents. In the present study, cicloprofen or diclofenac, representative of the arylalkanoic and anthranilic acids, respectively, augmented the antigen-dependent first stage and the calcium-dependent second stage of allergic histamine release. Both agents enhanced the rate and total amount of histamine release in the whole reaction. Further, it was demonstrated that augmentation could occur in a specific, non-cytolytic manner. In extended studies, cicloprofen and diclofenac augmented ionophore (A23187)- and concanavalin A-induced histamine release from human leukocytes and ionophore-induced release from rat mast cells. Concanavalin A- and ovalbumin-induced release from rat mast cells were inhibited by cicloprofen and diclofenac. These findings define systems useful for the study of the mechanisms of action of the acidic anti-inflammatory agents.

In vitro studies on the mechanism of action of a new antiallergic, Ro 21-7634.

The effects of Ro 21-7634 and disodium cromoglycate (cromoglycate) on the in vitro release of mediators of anaphylaxis from rat peritoneal cells and guinea pig lung tissue were compared. Ro 21-7634 was 25 fold more potent than cromoglycate as an inhibitor of antigen-induced histamine release from passively sensitized (IgE) rat peritoneal cells. Ro 21-7634 was also the more potent inhibitor of both compound 48/80- and concanavalin A-induced histamine release from rat peritoneal cells. The two drugs shared the common properties of producing the same maximal level of inhibition in each of the above releasing systems and exhibiting a time and concentration dependent loss of inhibitory activity when added to the cells prior to the releasing agent. Neither drug inhibited ionophore A23187-or ionophore X537A-induced histamine release from these cells. Ro 21-7634 inhibited antigen-induced (IgG1) histamine and SRS-A release from actively sensitized guinea pig lung fragments, whereas cromoglycate did not. The results indicate that Ro 21-7634 and cromoglycate act through a common mechanism to inhibit allergic mediator release and that Ro 21-7634 is the more potent inhibitor.

Concanavalin A stimulates phospholipid methylation and phosphatidylserine decarboxylation in rat mast cells.

When histamine release from rat peritoneal mast cells is stimulated by concanavalin A, membrane phospholipids are methylated in the early stage of this process. Exogenously added phosphatidylserine enhances the concanavalin A-induced histamine release, and at the same time the lectin markedly stimulates the decarboxylation and methylation of phosphatidylserine. Within minutes after the addition of concanavalin A to rat mast cells, the newly methylated phospholipids begin to disappear and an increased formation of lysophosphatidylcholine is observed. When rat mast cells are treated with concanavalin A in the absence of Ca2+, phospholipid methylation is stimulated but no significant release of histamine is detected. The subsequent exposure of the pretreated cells to Ca2+ causes increased release of histamine and degradation of methylated phospholipids. The inhibition of either synthesis or degradation of methylated phospholipids results in the inhibition of histamine release. These observations suggest that the synthesis and degradation of methylated lipids are an intrinsic part of the biochemical mechanism that modulate histamine release from mast cells.

Concanavalin A-Induced Histamine Release from Normal Rat Mast Cells

Concanavalin A- (con A) induced release of histamine from normal rat mast cells was studied. In the presence of phosphatidylserine (PS) con A induced a concentration and temperature-dependent, noncytotoxic histamine release at con A concentrations ranging from 0.1 to 100 mug/ml. The optimal con A concentration, 100 mug/ml, caused a 27.3% (+/- 2.7 S.E.M.) net histamine release. Release began approximately 30 sec after addition of con A and was complete within 45 min. In the absence of PS, no net con A-induced release occurred. The effect of PS was concentration dependent from 1 to 100 mgg/ml. PS alone, however, did not cause histamine release. Binding studies indicated that mast cells bound up to 16 X 10(6) con A molecules per cell without histamine release. Upon removal of unbound con A and the addition of PS, normal histamine release occurred. Alpha-Methyl-D-mannose (50 mM) prevented both con A binding and histamine release and if added after Con A, caused a rapid cessation of histamine release and a reversal of con A binding. This study indicates several important advantages of the con A-induced histamine release system. Binding of con A to mast cells can be dissociated from histamine release by omitting PS from the medium. Release can then be induced by the addition of PS. Alpha-Methyl-D-mannose can be used to terminate rapidly the ongoing release reaction at any phase of the interaction. This system is potentially very useful for investigation of metabolic events during histamine release.