Inhibition Of Passive Cutaneous Anaphylaxis Research Articles

Anti-inflammatory and anti-allergic activity of Jacareubin derivatives

Abstract Xanthone Jacareubin (JAC) isolated from heartwood of Calophyllum brasiliense has shown good anti-inflammatory against spike protein of SARS-CoV2 and anti-allergic activity. Methoxylated (Met) and acetylated (Ac) derivatives of JAC and its precursor xanthone V (X-V) were analyzed in this work to identify the structural functional groups that confer their biological activity. Met- and Ac-derivatives of JAC and X-V were synthesized and identified by 1H and 13C-NMR and MS. All compounds were evaluated for β-hexosaminidase degranulation (β-hex) of Bone Marrow Mast Cells. Both xanthones and Met-JAC derivative (3metJac) were evaluated on their inhibitory activity of xanthine oxidase (XO) and inhibition of passive cutaneous anaphylaxis (PCA). Also, both xanthones, 3metJac, and 4AcX-V were evaluated for inhibitory activity of Myeloperoxidase (MPO) and TPA-induced edema in mice. JAC showed better inhibition of β-hex than X-V, while Met-derivatives showed greater inhibitory activity on β-hex than JAC and X-V, but Ac-derivatives showed reduced inhibitory activity. Inhibition of XO and MPO of both xanthones showed the highest activity at 1 μmol/ear compared to Met- and Ac-derivatives evaluated. Also, both xanthones showed higher anti-inflammatory activity in the TPA-induced edema compared to the Met- and Ac-derivatives. While in the PCA, JAC and 3metJac showed similar inhibition and twice the inhibition of X-V and their derivatives. These results suggest that the fourth ring in the JAC is an important structural group for anti-allergic activity because X-V does not possess the fourth cyclized ring and has a fourth hydroxyl substituent group, showing poor inhibition of the allergic response. Supported by Conacyt Grant CF-2019-51488. Supported by Conacyt Grant CF-2019-51488

Novel findings in inhibition of mast cell-dependent immediate-type cutaneous reactions by Gahmi-Shini-San

This report describes an inhibitory effect of Gahmi-Shini-San (GSS) on mast cell-mediated immediate-type allergic reactions. GSS is an Oriental herbal medication, which has been successfully used in Korea for the treatment of allergic disorders, mainly skin anaphylactic diseases. GSS inhibited the ear swelling response induced by intradermal injection of compound 48/80 in a mouse model on a concentration-dependent basis. The mast cells in mouse ear tissue were stained by alcian blue/nuclear fast red. GSS significantly inhibited the compound 48/80-induced degranulation from mast cells in ear tissue. GSS dose-dependently inhibited the histamine release from the rat peritoneal mast cells by compound 48/80. We also studied the effect of GSS on mast cell-dependent passive cutaneous anaphylaxis activated by dinitrophenyl IgE antibody. GSS showed inhibition of passive cutaneous anaphylaxis following oral administration. These results indicated that GSS has inhibitory effect on mast cell-dependent immediate type cutaneous reactions.

Biological Activity of Rubia cordifolia and Isolation of an Active Principle

The present study deals with the isolation of mollugin, furomollugin and dehydro-a-lapchone from the chloroform fraction of Rubia cordifolia (Linn.) roots. Mollugin showed inhibition of passive cutaneous anaphylaxis (PCA) and protection of mast cell degranulation in rats. It also exhibited considerable activity against lymphoid leukemia (P338) in mice. Furomollugin and dehydro-a-lapchone were obtained for the first time from R. cordifolia.

O-77 - Gastric wall β2-adrenoceptor-mediated inhibition of passive cutaneous anaphylaxis (PCA) in rats

O-77 - Gastric wall β2-adrenoceptor-mediated inhibition of passive cutaneous anaphylaxis (PCA) in rats

Characterization of Allergoids from Ovalbumin in vitro and in vivo

Several in vivo and in vitro methods for monitoring immunological properties of two allergoids obtained by formaldehyde treatment of ovalbumin (OA) were developed. The calculated molecular weight of allergoids was 80 kD (OA-F1) and 165 kD (OA-F2), respectively. The allergenic activity in vitro of allergoids in mast-cell histamine release assay was 1000 times lower than of OA. Both allergoids showed reduced ability to induce passive cutaneous anaphylaxis in the Sprague- Dawley rats or systemic anaphylaxis in Dunkin-Harley guinea-pigs. The ability of OA and allergoids to bind to the OA-specific IgE antibodies was measured in vivo by the inhibition of passive cutaneous anaphylaxis (PCA-inhibition). Allergoid binding to IgE was 51–66% lower than the native allergen. Moreover, the avidity of OA-specific IgG antibodies, measured by ELISA-inhibition, for allergoids and allergen was of the same order. Allergoids induced a different pattern of humoral immune response from that, induced by the native allergen. Thus, after immunization of BALBIc mouse, both allergoids induced a higher production of IgG and a lower production of IgE than OA, only OA-F2 induced a lower production of IgG 1. The differences in the IgA response to the immunogens was not significant. Delayed hypersensitivity studies in the BALBlc mouse showed that allergoids were 5- to 12-times less effective in inducing a cell-mediated immune response than OA. The present study provides a battery of immunological methods for preclinical testing of modified allergens.

Inhibition of passive cutaneous anaphylaxis by synthetic human immunoglobulin E peptide fragments

In an attempt to determine the regions responsible for type 1 immediate hypersensitivity, a total of 42 peptide fragments, which cover the CH3CH4 domains in human immunoglobulin E (IgE), were chemically synthesized. Several peptide fragments located in the amino acid sequences Ala 329—Thr 357 and Arg 119—Ala 463, inhibited passive cutaneous anaphylaxis (PCA) in vivo. In order to pinpoint the sites responsible for the inhibition of the PCA reaction, various rragment peptides in these two regions were synthesized. As a result, residues Pro 343—Leu 348, Pro 426—Thr 433, and Ser 456—Thr 401 were suggested to be involved in type I immediate hypersensitivity.

Inhibition of passive cutaneous anaphylaxis by several histamine (H1) and serotonin antagonists in the rat.

Drugs of the pizotifen type (pizotifen, cyproheptadine), possessing high H1-antihistamine and high antiserotonin activities in animal experiments, exert potent inhibitory actions on the passive cutaneous anaphylaxis (PCA) reaction in the rat. The drug pipethiadene, a 4,9-dihydrothieno(2,3-c)-2-benzothiepin derivative also belongs to this group. Selective histamine H1-antagonists alone are unable to cause pronounced reduction of the intensity of the PCA reaction in the rat, but in local reactions induced in rats by compound 48/80, histamine H1-receptors seem to play major role.

Recombinant human IgE.

The gene for a human epsilon chain Fc fragment has been cloned and expressed at a high level in Escherichia coli, and its biological activity in binding to the high-affinity receptors on mast cells and basophils and mediating histamine release has been examined in a variety of assays, including the inhibition of passive cutaneous anaphylaxis in human skin, which was induced by ragweed immunoglobulin IgE antibody and antigen. The positive results obtained in these assays encouraged us to try to analyse the binding site on IgE by site-directed mutagenesis. We describe deletion mutants here that narrow down the binding site on IgE for the mast cell receptor to a stretch of 76 amino acids (residues 301-376 on the ND epsilon chain) spanning the CH2 and CH3 domains. This peptide displays activity in the human skin test indistinguishable from that of a myeloma IgE.

Inhibition of passive cutaneous anaphylaxis (PCA) by azelastine: dissociation of its antiallergic activities from antihistaminic and antiserotonin properties.

Azelastine and methysergide injected i.v. 5 min prior to antigen challenge and disodium cromoglycate (DSCG) injected i.v. immediately before antigen challenge produced dose-dependent inhibition of IgE-mediated 72 h passive cutaneous anaphylaxis (PCA) responses with ID50S of 0.3, 0.2 and 1.0 mg/kg, respectively. Thus, azelastine is about three times as effective as DSCG (a mast cell stabilizing agent) and somewhat less active than methysergide (a specific serotonin "D" receptor antagonist). Oral administration of azelastine and other drugs 2 h prior to antigen challenge produced strong inhibitory effects on PCA. The ID50S (mg/kg) were as follows: azelastine = 1.4; astemizole = 1.6; ketotifen = 2.0; aminophylline = 4.6; and diphenhydramine = 10.9. After 4 h of oral administration, azelastine and other drugs inhibited PCA responses with the following ID50S (mg/kg): azelastine = 1.8; astemizole = 2.3; ketotifen = 2.3; and aminophylline = 12.5. Azelastine administered orally 24 h before antigen challenge was still capable of exerting significant anti-PCA activity with an ID50 of 2.6 mg/kg, whereas none of the other drugs tested produced any significant inhibitory effects on PCA. In subsequent experiments, it was established that the antiallergic and antihistaminic activities of azelastine are inseparable 2 h after oral administration (ID50 of azelastine mg/kg, p.o., 2 h: PCA = 2.6 and histamine = 3.1). However, the persistence of the oral antiallergic (anti-PCA) effects of azelastine for 24 h (ID50 = 3.7 mg/kg) does not seem to be associated with its antihistaminic or antiserotonin activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of passive cutaneous anaphylaxis by compounds of Camellia sinensis.

Caffeine, theophylline, theobromine, (+) catechin, (-) epicatechin, gallic acid and theaflavin obtained from black tea (Camellia sinensis) inhibit passive cutaneous anaphylactic reaction in mice without affecting acetylcholine, histamine and serotonin induced broncho-constriction in the guinea pig. Theophylline and theaflavin antagonise only prostaglandin F2 alpha induced bronchoconstriction.

On the Latency Period of Sensitization: Inhibition of Passive Cutaneous Anaphylaxis by a Factor in Normal Rat Serum

Addition of normal rat serum to mouse or rat IgE antibody blocks the passive cutaneous sensitization of rats with either IgE. The inhibition can be obtained with isologous and autologous rat serum. The blocking factor was purified and characterized as a molecule with a MW of 69,000 daltons, a sedimentation rate of 4.5 s and an isoelectric point of pH 4.7. The factor blocks the PCA reaction also at previously sensitized skin sites and seems to act on the secretory phase of mediator release.

Characterisation of the reaginic response to sulphonamides in mice.

Reaginic responses were induced in immunised mice with either 4-sulphanilamidobenzoic acid (4-SABA) or sulphamethoxazole (SMX) coupled to chicken gamma-globulin (CGG). The former was coupled through the carboxylic group of benzoic acid and the latter through the diazo derivative of the sulphanilamide group. The specificity of the reaginic responses obtained was assessed in each case by inhibition of passive cutaneous anaphylaxis in the rat. Immunisation with 4-SABA-CGG resulted in antibodies which recognised the sulphanilamide group as immunodominant and, therefore, they cross-reacted strongly with other sulphonamides. In contrast, SMX-CGG-induced IgE antibodies directed primarily to the methoxazole end of the molecule and cross-reactivity with other sulphonamides could not be demonstrated. This model may be useful for a more comprehensive study of allergic reactions induced by sulphonamides.

Inhibition of passive cutaneous anaphylaxis by dipeptides

The action of some dipeptides (Lalpha-alanyl-histidine, Lbeta-alanyl-histidine, histidyl-leicine and glycyl-histidine), and histidine on passive cutaneous anaphylaxis of guinea pigs was studied. Lbeta-alanyl-histidine (karnosine) and Lalpha-alanyl-histidine proved to inhibit the passive cutaneous anaphylaxis. Histidyl-leicine, glycyl-histidine, and histidine failed to produce any inhibitory effect on passive cutaneous anaphylaxis.

Characterization of the target cell receptor for IgE—I. Solubilization of IgE-receptor complexes from rat mast cells and rat basophilic leukemia cells

Purified rat monoclonal IgE was labeled with 125I and allowed to interact with either purified rat mast cells (RMC) or rat basophilic leukemia cells (RBL). Virtually 100% of the cell bound 125I-IgE was solubilized by treating the cells with buffer containing 0.5% Nonider P-40. When this solubilized IgE was subjected to gel filtration it was found to elute ahead of free IgE or IgE which had been allowed to interact with control (non-IgE binding) cells, indicating that at least a portion of the cellular IgE receptor remained attached to the IgE. The IgE-receptor complexes isolated from either cell type eluted at almost identical volumes, and a comparison with polymeric IgA suggested that they had a mol. wt of 3·5–5·5 × 10 5 daltons. Complex formation also occured if cells were solubilized prior to the addition of IgE. Soluble cell extracts from both RMC and RBL cells caused inhibition of passive cutaneous anaphylaxis, however, the inhibition was less efficient than that given by comparable numbers of intact cells.

Inhibition of immediate hypersensitivity reactions in laboratory animals by a phenanthroline salt (ICI 74,917).

1. The activity of a new anti-allergic compound, I.C.I. 74,917, has been studied in the rat, mouse and guinea-pig. 2. Following intravenous administration, I.C.I. 74,917 inhibits in a dose-dependent manner passive cutaneous anaphylaxis induced in rats and mice by heat-labile homocytotropic antibody. In rats, its potency is approximately 300 times that of disodium cromoglycate. 3. To achieve maximal inhibition, it is necessary to administer I.C.I. 74,917 at the same time as antigenic challenge; dosing before or after challenge has much less effect. 4. Liberation of histamine, provoked by the antigenic challenge of mast cells passively sensitized in vitro by IgE-like antibody, is reduced in the presence of I.C.I. 74,917. 5. Intravenous administration of the compound has no significant effect upon local blueing reactions provoked in the rat by intradermal injection of histamine, 5-hydroxytryptamine or Compound 48/80. It has only a slight effect at high doses upon passive cutaneous anaphylaxis induced in the rat by heat-stable homocytotropic or heterologous (guinea-pig) antibodies. 6. Although not a bronchodilator in the guinea-pig, I.C.I. 74,917 partially inhibits systemic anaphylaxis. A consistent reduction in the severity of antigen-induced bronchospasm was demonstrated in the Konzett-Rossler preparation at doses comparable to those inhibiting passive cutaneous anaphylaxis in the rat. However, there was only slight inhibition of passive cutaneous anaphylaxis in the guinea-pig. 7. I.C.I. 74,917 itself induces bronchospasm when administered to anaesthetized guinea-pigs or to a guinea-pig isolated lung preparation. This effect is reversed by salbutamol, but is not prevented by the prior administration of mepyramine, atropine or methysergide. 8. These results indicate that in the rat, mouse and guinea-pig, I.C.I. 74,917 is a potent inhibitor of certain types of immediate hypersensitivity reactions.