Inhibition Of Anaphylaxis Research Articles

Nanocarrier-mediated Inhibition of Anaphylaxis via Targeting Siglec-6 Receptors

CD33-family Siglec receptor engagement has been demonstrated to have inhibitory effects on various cells including mast cells. Nanocarriers are nanoscale vehicles that can transport and present bioactive molecules on their surfaces at controllable densities. We therefore hypothesized that using targeted nanocarriers to orchestrate selective engagement of Siglec-6, predominantly expressed on mast cells, would inhibit anaphylaxis in mice.

Inhibition of anaphylaxis like reaction and mast cell activation by Sitagliptin

Mast cells stimulation activates degranulation process resulting in releasing of mediators, such as histamine. In this study, the effect of aqueous extract of sitagliptin, a selective dipeptidylpeptidase-4 inhibitor, on the mast cell-mediated allergic response was studied with the possible mechanisms of action, focusing on the histamine release and pro-inflammatory cytokine secretion in mast cells. Sitagliptin produced dose dependent inhibition in compound 48/80-induced systemic reactions. In addition, sitagliptin attenuated IgE-mediated skin allergic reaction. Sitagliptin dose-dependently reduced compound 48/80- and IgE-induced histamine release from mast cells. Sitagliptin decreased the secretion of pro-inflammatory cytokines, tumor necrosis factor-α, in mast cells. So, the finding of this study provides evidence that sitagliptin inhibits mast cell derived allergic reactions, and involvement of pro-inflammatory cytokine secretion in such effects.

Optimized ultrasonic-assisted extraction of flavonoids from Prunella vulgaris L. and evaluation of antioxidant activities in vitro

Abstract The Box–Behnken design combined with response surface methodology was used to optimize ultrasonic-assisted extraction of total flavonoids from Prunella vulgaris L. The results indicated that the highest extraction yield of flavonoids by ultrasonic-assisted extraction could obtain to be 3.62% using ethanol concentration of 41% (v/v) as solvent and liquid to solid ratio of 30:1 (mL/g) for 30.5 min at the temperature of 79 °C. The crude extract was then purified by AB-8 macroporous adsorption resin, the flavonoids content in the purified extract increased to 81.58%. The antioxidant activities of the purified flavonoids were evaluated in vitro by scavenging capability of DPPH free radical and hydroxyl free radical, reducing power, total antioxidant capability and β-carotene bleaching test. The results showed that the flavonoids have significant antioxidant activities, which can be used as a source of potential antioxidant. Industrial Relevance The effective exploitation and application of the natural plant resources have very important significance for the industrial and economic development. Prunella vulgaris L. is a perennial plant commonly found in China and Europe, which was proved to be rich in flavonoids, triterpenes and phenolic acid. It has long been used as a folk medicine for alleviating sore throat, reducing fever and accelerating wound healing. Recent studies have demonstrated that the methanol or water extract of this herb exhibits many of the activities including antihyperglycemic activity, systemic anaphylaxis inhibition, antioxidative antiviral and antibacterial effects. However, attempts have not been made so far to investigate the ultrasonic-assistant extraction of flavonoids from P. vulgaris L. and evaluate their antioxidant activities in vitro. In this work, a four-variable, three-level experiment Box–Behnken design based on response surface methodology was used to optimize ultrasonic-assistant extraction of flavonoids from P. vulgaris L. The optimized results showed that the highest extraction yield of flavonoids by ultrasonic-assisted extraction could arrive 3.62%, using 41% (v/v) ethanol as solvent and 30:1 (mL/g) liquid to solid ratio for 30.5 min at the temperature of 79 °C. The suitability of the model equation for predicting the optimum response values was tested using the selected optimal conditions. The predicted extraction yield of flavonoids was 3.63%, which was consistent with the practical extraction yield of flavonoids of 3.62%. The crude extract was then purified by AB-8 macroporous adsorption resin, the flavonoids content in the purified extract increased to 81.58%. The antioxidant activities of the purified flavonoids were evaluated in vitro by scavenging capability of DPPH free radical and hydroxyl free radical, reducing power, total antioxidant capability and β-carotene bleaching test. The results indicated that the flavonoids have significant antioxidant activities, which can be used as a source of potential antioxidant or functional food material. We believe that the knowledge gained from this study should be helpful to further exploit and apply this resource .

IgG-blocking antibodies inhibit IgE-mediated anaphylaxis in vivo through both antigen interception and Fc RIIb cross-linking

Although it has long been hypothesized that allergen immunotherapy inhibits allergy, in part, by inducing production of IgG Abs that intercept allergens before they can cross-link mast cell Fc epsilonRI-associated IgE, this blocking Ab hypothesis has never been tested in vivo. In addition, evidence that IgG-allergen interactions can induce anaphylaxis by activating macrophages through Fc gammaRIII suggested that IgG Ab might not be able to inhibit IgE-mediated anaphylaxis without inducing anaphylaxis through this alternative pathway. We have studied active and passive immunization models in mice to approach these issues and to determine whether any inhibition of anaphylaxis observed was a direct effect of allergen neutralization by IgG Ab or an indirect effect of cross-linking of Fc epsilonRI to the inhibitory IgG receptor Fc gammaRIIb. We demonstrate that IgG Ab produced during the course of an immune response or administered passively can completely suppress IgE-mediated anaphylaxis; that these IgG blocking Abs inhibit IgE-mediated anaphylaxis without inducing Fc gammaRIII-mediated anaphylaxis only when IgG Ab concentration is high and challenge allergen dose is low; that allergen epitope density correlates inversely with the allergen dose required to induce both IgE- and Fc gammaRIII-mediated anaphylaxis; and that both allergen interception and Fc gammaRIIb-dependent inhibition contribute to in vivo blocking Ab activity.

Minor role of the C3a receptor in systemic anaphylaxis in the guinea pig

Previously, Regal et al. [Regal, J.F., Fraser, D.G., Toth, C.A., 1993. Role of the complement system in antigen-induced bronchoconstriction and changes in blood pressure in the guinea pig. J. Pharmacol. Exp. Ther. 267, 979–988] demonstrated that preventing complement system activation resulted in inhibition of anaphylaxis in the guinea pig, and that the C-terminal 21 amino acids of guinea pig C3a (C3a-peptide) mimic the symptoms of anaphylactic shock in the guinea pig [Regal, J.F., 1997. Role of the complement system in pulmonary disorders. Immunopharmacology 38, 17–25]. To determine if C3a is an essential mediator of systemic anaphylaxis, the anaphylactic response to ovalbumin (OA) was assessed in guinea pigs genetically deficient in the C3a receptor (C3aR−) compared to their control strain of animals which were C3a receptor positive (C3aR+). In addition, the response to another control strain of animals, Hartley guinea pigs, was determined. Sensitized guinea pigs were anesthetized, and bronchoconstriction and changes in blood pressure were monitored in response to intravenous (i.v.) injection of either C3a-peptide, recombinant human C5a (rHuC5a) or OA. Both Hartley guinea pigs and C3aR+ animals responded similarly to C3a-peptide and rHuC5a. C3aR− animals, however, were unresponsive to C3a-peptide and responded normally to rHuC5a, confirming their functional deficiency of the C3a receptor. In response to OA, C3aR+ animals and Hartley guinea pigs responded with a severe bronchoconstriction, an initial transient hypotension, followed by an increase in blood pressure and a delayed prolonged hypotensive response. In contrast, in C3aR− animals, the increased blood pressure response to OA was significantly prolonged, the delayed hypotensive response was blunted, and the bronchoconstriction was delayed compared to the C3aR+ animals. The difference in the anaphylactic response could not be explained by differing amounts of OA-specific IgG1 antibody or C3a generated during the anaphylactic response. Thus, these data suggest that C3a plays a minor role in the hypotension of systemic anaphylaxis and investigation of a role for other products of complement system activation, either alone or in combination with C3a, is clearly warranted.

Inhibition of Anaphylaxis by Sulfasalazine in Rats

We studied the effect of sulfasalazine on anaphylaxis. Sulfasalazine dose-dependently inhibited systemic anaphylaxis induced by compound 48/80 in rats. Sulfasalazine also inhibited local anaphylaxis activated by anti-dinitrophenyl (anti-DNP) IgE. Moreover, sulfasalazine dose-dependently inhibited histamine release in the peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. All of these effects were comparable to those of the disodium cromoglycate (reference drug) tested. When sulfasalazine was added, the level of cAMP in rat peritoneal mast cells transiently and significantly increased about 6-fold compared with that of basal cells. Our studies provide evidence that sulfasalazine may be beneficial in the treatment of anaphylaxis.

Cross-reactivity of ovine IgE with anti-human IgE.

Cross-reactivity between ovine and human IgE was investigated using monoclonal antibodies to human IgE heavy chain. Western immunoblotting, reverse cutaneous anaphylaxis (RCA), passive cutaneous anaphylaxis inhibition (PCAI) and reverse passive cutaneous anaphylaxis (RPCA) tests were all used to assess cross-reactivity between the monoclonals and ovine IgE. No cross-reactivity was demonstrated using Western immunoblotting, RCA and PCAI tests. However, evidence for homology in the region of the molecule concerned with mast cell binding was demonstrated by RPCA performed in sheep skin primed with human myeloma IgE.

Isolation of porcine IgE, and preparation of polyclonal antisera

High Titre, Ascaris specific, porcine reaginic antibody was induced by combining parasitic infestation and antigen challenge. The reagin was characterised as being heat labile at 56°C, possessing long term skin sensitising activity, and as having physicochemical properties similar to IgE in other species. Porcine IgE was purified by conventional immunochemical techniques, and an ϵ chain isolate prepared using SDS-PAGE gel excision and electro elution. Antisera raised against the intact IgE molecule and its ϵ chain were rendered monospecific by immunoabsorption and characterised by reverse cutaneous anaphylaxis (RCA) testing, passive cutaneous anaphylaxis inhibition, immunohistology and Western blotting. These antisera are currently being used to study the regulation of IgE responses in the pig.

Inhibition of anaphylaxis by inactivated lymphocyte clone with radiolabelled antigen.

125I-labelled ovalbumin (OVA) antigen did not sensitize guinea-pigs and anaphylaxis did not develop after native OVA challenge. The radiolabelled antigen was fixed by lymphocytes with highly specific receptors for 125I-OVA and this condition produced a continuous radiation damage leading to inactivation of the cells. As the proliferative response of lymphocytes did not occur, no antibody production was detected. This was demonstrated by passive haemagglutination techniques. However, the immune response to a simultaneously given non-radioactive antigen remained intact. It is supposed that radiation damage depended on specific activity of antigen destroying the antigen-specific lymphocyte clone selectively. The mechanism and the practical importance of the in vivo 'antigen suicide' is discussed.

Studies on the allergenic structure of hen ovomucoid by chemical and enzymic fragmentation.

The allergenic structure of ovomucoid was studied by fragmentation with cyanogens bromide and Staphylococcal protease. Two fragments obtained by cyanogen bromide cleavage were identified in the primary structure of ovomucoid to be peptide 1-68 and peptide 69-186 cleaved at position 84 and linked together by a disulfide bridge between 70 and 109. Allergenic activity, assayed by a passive cutaneous anaphylaxis inhibition test using IgE antibody from mouse, was retained only in peptide 69-186. Three fragments obtained by Staphylococcal protease digestion corresponded to peptide l-130 and two peptides 131-186 differing in carbohydrate content. Only peptide 1-130 was allergenic. The trypsin binding ability remained only in the allergenic peptides. These results suggest that either the common peptide portion in 1-130 and 69-186 or a long range structure composed of these peptides is essential for allergenic activity.

A new method of allergen standardization: Passive cutaneous anaphylaxis inhibition in a mouse-to-rat system in comparison with other methods

Various methods have been employed for standardization of potency of allergen extracts. We used passive cutaneous anaphylaxis (PCA) inhibition in a mouse-to-rat system as a new means of standardization. Several allergen extracts, including mite, short ragweed, house dust, Aspergillus, Candida, and Japanese cedar, were examined. Mouse IgE antibodies were produced after two or three injections of antigen and alum. The potency measured by PCA inhibition in the mouse-to-rat system was compared with that of protein nitrogen (PN) content, end point of prick test in humans, and 50% radioallergosorbent test (RAST) inhibition. Our studies suggest that the mouse-to-rat system could be used to determine allergenic potency and to standardize allergen extracts.

Interrelationship of cyclic nucleotides and anaphylactic reactions.

THE mode of action of several anti-allergic drugs, which are structurally diverse, has been studied by comparing their inhibition of cyclic nucleotide phosphodiesterase with inhibition of anaphylaxis. The cyclic nucleotide phosphodiesterase activities were measured in microsomal preparations of both human and sheep lung, and the anaphylaxis was observed in vitro in passively sensitised human lung and in rats in vivo (passive cutaneous anaphylaxis (PCA)). A significant correlation has been found between the inhibition of anaphylaxis and the ratio of the inhibition of hydrolysis of cyclic AMP to the inhibition of hydrolysis of cyclic GMP. A less significant correlation was also found between inhibition of rat PCA and inhibition of hydrolysis of cyclic GMP.

Immunological Cross-Reactivities between Two Yeast Cytochromes c and the Immunological Reactivities of the Peptide Fragments of Saccharomyces oviformis M<SUB>2</SUB> Cytochrome c

Cytochromes c from two strains of yeast, Saccharomyces oviformis M2 (M2-cyt. c) and Candida krusei, in their cross-reactivities against their antibodies, were investigated by various methods. The results indicated that cytochromes c from these two yeasts cross-reacted each other with their antibodies, but that horse heart cytochrome c did not cross-react. It was also suggested that the passive cutaneous anaphylaxis inhibition test is preferable to the usual in vitro methods in detecting slight difference in the cross-reactivities between closely related antigens. Another experiments using peptide fragments obtained by enzymatic or chemical cleavage of M2-cyt. c showed that P-4 and P-7 were found to fix complements, and P-3, P-4, P-5 and P-6 eliminated the inhibitory effect of the antibody against the enzymatic reaction of cytochrome c-cytochrome oxidase.

Antigen Excess in Guinea Pig Anaphylaxis

Summary Systemic anaphylaxis in passively sensitized guinea pigs failed to occur when the animals were challenged with massive doses (0.5 to 1.0 g) of protein antigen intracardially. In the isolated sensitized guinea pig lung, bronchospasm was diminished or absent when large amounts of antigen were used for perfusion. PCA in guinea pig skin passively sensitized with rabbit anti-DNP sera was markedly reduced when large concentrations of divalent DNP haptens (bis-DNP lysine and bis-DNP ornithine) were employed. These observations suggest that the inhibition of anaphylaxis by large concentrations of antigen may depend upon the formation in vivo of “nontoxic” complexes of composition Ag2Ab.

Inhibition of anaphylaxis in mice by pre-treatment with cysteine, lysine ethyl ester, and tyrosine ethyl ester

L'injection intraperitoneale chez la souris de cysteine, tyrosine-ethylester ou lysine-ethyl-ester, 1 h avant la production du choc anaphylactique diminue d'une facon significative la sensibilite des animaux a la reaction. Il est possible que cela soit du a une modification de l'effet du premier compose actif du complement.

Passive Anaphylaxis in the Guinea Pig and Its Inhibition by an Extraneous Antigen-Antibody Reaction

Summary Relationships of antigen and antibody concentration have been studied in passive anaphylaxis of the guinea pig challenged by aerosol. Inhibition of anaphylaxis in sensitized animals by an unrelated antigen and antibody has been found to be dependent on concentration. Injection of washed aggregates of the unrelated system was ineffective although the same small reduction of serum complement was produced as with the effective method of separately injecting antigen and antibody. Administration of serum previously treated in vitro with extraneous antigen and antibody also produced refractoriness to challenge. The kinetic relationships of antigen and antibody and the possible role of serum factors in anaphylaxis and in the inhibition of anaphylaxis have been discussed.

Inhibition of anaphylaxis in the guinea pig by local streptococcal infection: The influence of adrenalectomy

1. 1. Guinea pigs infected locally with a group C streptococcus developed refractoriness to anaphylaxis after a suitable induction period. Bilateral adrenalectomy of guinea pigs after infection but forty-eight hours before challenge had no effect on the manifestation of hyporesponsiveness. 2. 2. Surgical trauma did not reduce passively induced hypersensitivity. 3. 3. Infection in adrenalectomized animals did not alter the histamine sensitivity of the tissues.

Comparative inhibition of anaphylaxis in mice by steroids, tranquilizers and other drugs.

The physiological mechanisms involved in anaphylaxis were further investigated by studies of drugs with adrenolytic, hypertensive, vasoconstrictive action, also tranquilizers and antihistaminics, diuretics, anti-inflammatory agents and newly available steroids. Mice were sensitized with normal horse serum. All drugs were administered prior to challenge and protection gauged by survival of sensitized mice compared with incidence of fatal anaphylaxis in untreated sensitized mice. Compounds exerting maximum protection were chlorpromazine, promazine, reserpine, lysergic acid diethylamide, prednisolone, prednisone, fluorohydrocortisone, hydrocortisone and cortisone. Inactive compounds were meprobamate, sedatives and antihistaminics, inflammatory agents, diuretics and predominantly sodium-retaining steroids.

ヂフテリア毒素から分劃したアナフイラキシー阻止物質に関する研究

ヂフテリア毒素から分劃したアナフイラキシー阻止物質に関する研究

Inhibition of Anaphylaxis in Guinea Pigs by D-Catechin

Inhibition of Anaphylaxis in Guinea Pigs by D-Catechin