Homologous Passive Cutaneous Anaphylaxis Research Articles

Inhibition of homologous passive cutaneous anaphylaxis (PCA) by disodium cromoglycate-related compounds.

A study was conducted to examine the effect on homologous PCA in rats of 14 different, newly synthesized compounds, given orally, in relation to the chemical structure of DSCG, when given orally on homologous PCA in rats. The structure-activity relationship of these compounds was also discussed. Among the 7 compounds of the glycerol bischromenonyl ether derivatives, 1,3-bis (2-phenyl-4-chromenon-5-yl) oxypropane-2-ol (compound 1) showed the most potent inhibitory activity on PCA. The other compounds showed a moderate or no effect. Two compounds of glycerol bisphenyl ether derivatives had little effect. On the other hand, 1,3-bis (2-carboxy-3-hydroxyphenyl)oxypropane (compound 11) out of alkandiol bisphenyl ether derivatives significantly inhibited PCA, and the other 4 compounds showed a tendency toward inhibition of the reaction. The late inhibition, seen in the biphasic inhibitory pattern induced by compound 11, may be caused by a certain active substance transformed in the body.

Antigenicity of Casein Enzymatic Hydrolysate

An enzymatic hydrolysate of bovine casein was studied for molecular size and antigenic properties. As determined by Sephadex G-25 gel filtration, polypeptide fractions having molecular weights greater than 1,000 were not detected in the soluble fraction of the casein hydrolysate. Antigenicity of the fraction was not detected by heterologous passive cutaneous anaphylaxis in guinea pig-rabbit antiserum system mediated by immunoglobulin G types of antibody (guinea pig passive cutaneous anaphylaxis) and its inhibition test. Furthermore, it was not detected by rat long latency homologous mediated by immunoglobulin E antibody and its inhibition test. To prepare anti-casein immunoglobulin E serum for rat long latency homologous passive cutaneous anaphylaxis, immunization of rats was by single subcutaneous injection of casein with aluminum hydroxide. Antiserum with highest passive cutaneous anaphylaxis titer (1:64) against bovine casein was obtained by a dose of 2,000μ of the protein at day 12.

Effect of 6-Ethyl-3-(1H-Tetrazol-5-YL)Chromone (AA-344) on the Immediate and Delayed Hypersensitivity Reactions

Effects of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) on the experimental models of the type I-IV allergic reactions were studied in comparison with those of disodium cromoglycate (DSCG), dexamethasone and other agents. AA-344 showed inhibitory effects on the homologous passive cutaneous anaphylaxis and the passive systemic anaphylaxis in guinea pigs. However, it had only a slight or little effect on the Forssman shock in guinea pigs, the complement-dependent cytolysis of mast cells in rats, the Arthus reaction in guinea pigs and the tuberculin reaction and the contact sensitivity in mice. DSCG was less effective, using these experimental models. Dexamethasone showed a suppressive effect on the type III and IV allergic reactions. The results indicate that AA-344 selectively suppresses the type I allergic reaction.

Effect of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) on the immediate and delayed hypersensitivity reactions.

Effects of 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) on the experimental models of the type I-IV allergic reactions were studied in comparison with those of disodium cromoglycate (DSCG), dexamethasone and other agents. AA-344 showed inhibitory effects on the homologous passive cutaneous anaphylaxis and the passive systemic anaphylaxis in guinea pigs. However, it had only a slight or little effect on the Forssman shock in guinea pigs, the complete-dependent cytolysis of mast cells in rats, the Arthus reaction in guinea pigs and the tuberculin reaction and the contact sensitivity in mice. DSCG was less effective, using these experimental models. Dexamethasone showed a suppressive effect on the type III and IV allergic reactions. The results indicate that AA-344 selectively suppresses the type I allergic reaction.

A canine model for reaginic hypersensitivity and allergic bronchoconstriction

Immunization of neonatal dogs with a conjugate of 2,4-dinitrobenzene and ovalbumin (DNP 2-OA), using aluminum hydroxide as the adjuvant, elicited long-lasting (over 30 wk) anti-DNP and anti-OA IgE antibody responses of high titers as determined by homologous passive cutaneous anaphylaxis. Low antigen doses of 10 or 50 μg were more effective than the higher doses of 250 or 1,250 μg in inducing high IgE antibody levels. However, this method of immunization failed to elicit any detectable IgE antibody response in adult dogs. Bronchoprovocation with antigen of sensitized animals having IgE antibody titers in excess of 64 resulted in a marked increase in airflow resistance, which could be corrected by the administration of nebulized isoproterenol. On the other hand, sensitized animals with IgE antibody titers in the order of 64 did not manifest significant bronchoconstriction on inhalation challenge but developed anaphylaxis following intravenous injection of the antigen.

ChemInform Abstract: BENZODIPYRAN DERIVATIVES WITH ANTIALLERGIC ACTIVITY

AbstractZur Untersuchung auf antiallergische Wirkung werden zahlreiche Benzodipyrane untersucht.

Benzodipyran derivatives with antiallergic activity

The synthesis and antiallergic activity of a number of benzodipyrandicarboxylic acids are described. Antiallergic activity of the compounds was determined using the homologous passive cutaneous anaphylaxis (PCA) reaction in the rat. The structural requirements for activity in the PCA screen are discussed. In this test system the linear benzodipyrans are more active than their angular analogues.

Properties of mouse homocytotropic and heterocytotropic antibodies

Mouse antisera were analyzed for the presence of homocytotropic and heterocytotropic antibodies. Two distinct populations of antibodies were detected by the homologous passive cutaneous anaphylaxis (PCA) reaction. The first was active 2 hr after injection, heat-stable, and partially reactive with antisera to mouse IgG 1. The second was active 48 hr after injection, was heat-labile, and probably belonged to the IgE class of mouse immunoglobulins. In addition, it was demonstrated that there were also two antibodies active in the heterologous PCA reaction in rats, a heat-stable antibody and a heat-labile antibody. Contrary to results obtained with homocytotropic antibodies, none of the heterocytotropic antibodies detected reacted with antisera to mouse IgG 1 or IgG 2. These studies suggest that in addition to IgE there may exist another heterocytotropic antibody in mouse antisera and that caution should be employed when using the 2-hr PCA reaction in the rat as a sole criterion for detection of mouse IgE.

Inhibition of hypersensitivity reactions by a new drug, N(3′,4′-dimethoxycinnamoyl) anthranilic acid (N-5′)

N(3′,4′-dimethoxycinnamoyl) anthranilic acid (N-5′), a new antiallergic drug, can be taken orally, has low toxicity, and is a potent inhibitor of homologous passive cutaneous anaphylaxis (PCA) both in rats and in guinea pigs. Anaphylactic mediator release from guinea pig lung was decreased by the drug in vitro. Although reversed cutaneous anaphylaxis and Arthus type reactivity were moderately inhibited with N-5′, this agent did not inhibit the Forssman systemic reaction or contact dermatitis. N-5′ is considered to be clinically applicable to certain allergic-related diseases, in particular asthma caused by reaginic antibody.

Acute hypersensitivity pneumonitis in the rabbit. I. An animal model with horseradish peroxidase as antigen.

An experimental model of acute hypersensitivity pneumonitis was developed in rabbits using horseradish peroxidase as antigen. The lesion, produced by aerosol challenge with horseradish peroxidase 21 days after a single parenteral immunization with horseradish peroxidase and complete Freund adjuvant, was characterized by diffuse infiltration of respiratory bronchioles and of alveolar ducts and walls with approxomately equal numbers of mononuclear cells (lymphocytes and macrophages) and polymorphonuclear cells. This lesion, which was specific for the antigen, was distinct from the variable granulomatous component that was directly attributable to the use of complete Freund adjubant. Development of the lesion did not correlate with the humoral immune response, as indicated by antigen-binding, precipitin, and homologous passive cutaneous anaphylaxis assays, by negative serum transfer studies, by lack of correlation with immediate and intermediate Arthuslike) skin reactivity, by absence of electron microscopic and immunofluorescent evidence for immune complex processes, and by lack of evidence for complement activation. Development of the lesion did correlate with delayed (12- to 48-hour) skin reactivity, although rigid identification of cell-mediated immunity was not possible on histologic examination.

Reaginic antibody productions in rabbits and rats infected with Angiostrongylus cantonensis.

Angiostrongylus cantonensis-infected rabbits and rats were monitered for the productions of reaginic and indirect hemagglutinating (IHA) antibodies. Rabbit reaginic antibody detected by 72 hour homologous passive cutaneous anaphylaxis (PCA) was first demonstrated in sera of rabbits infected with 230 infective larvae 9 weeks after primary infection and persisted at very low titers for considerable duration. When such rabbits were reinfected with 600-820 larvae on Day 36, the reaginic antibody occurred much earlier, i.e., as early as 6 weeks after primary infection. The secondary and tertiary infections markedly boosted the PCA titers which gradually declined thereafter. Rabbit reaginic antibody was heat resistant but other physico-chemical properties were analogous to human IgE. No substantial IHA antibody productions were observed in sera of the infected Tabbits. A peak reaginic antibody response in rats was observed 5 weeks after primary infection. However, the reaginic antibody production in rats was only transient and no anamnestic response was induced by reinfection. In rats, IHA antibody was first detected in sera as early as 6 weeks postinfection and persistently observed throughout 6 to 18 weeks postinfection. Reinfections significantly boosted the IHA titers in some rats but not in the others.

Angiostrongylus cantonensis: lymphoid cell responsiveness and antibody production in rats.

Angiostrongylus cantonensis-infected rats were examined for the presence of antigen sensitive lymphocytes, as assessed by the in vitro uptake of tritiated thymidine by cells of various lymphoid organs (cervical, mediastinal and mesenteric lymph nodes, spleen and periphereal blood), following stimulation by adult worm antigen. The lymphoid cell response of rats to A. cantonensis appeared to be local in nature in that significant responses were noted only in the cervical lymph node cells during the first 4 weeks of infection. The responses of spleen cells to phytohemagglutinin gradually declined as the infection progressed and this reduced responsiveness was statistically significant during the period of 5 to 10 weeks of infection. Homocytotropic antibody, demonstrated by 72-hour homologous passive cutaneous anaphylaxis, was detected throughout 2 to 17 weeks postinfection with a peak response at the 5th week of infection. The antibody was heat labile and sensitive to reduction by 2-mercaptoethanol and alkylation. Hemagglutinating antibody was first observed 5 weeks after infection and high titers occurred throughout 6 to 17 weeks postinfection.

Demonstration and Interspecies Cross-Sensitization of Reaginic Antibodies in Dogs Infected with Dirofilaria Immitis *

Dogs infected with Dirofilaria immitis produced at least two types of skinsensitizing antibodies detectable by homologous passive cutaneous anaphylaxis (PCA) using adult soluble antigens. Reaginic antibodies (IgE-like) were demonstrated in 15 out of 36 dogs (42%) using 48- to 72-hour skin sensitization periods. Short term skin-sensitizing antibodies were found in 17 out of 36 dogs (47%) with 2- to 3-hour latent periods. The IgE-like reaginic antibodies were inactivated at 56°C for 4 to 6 hours. They were capable of inducing PCA reactions in the skin of rabbits and to a lesser extent in the skin of rhesus monkeys but not of guinea pigs and rats. No precipitating antibodies were demonstrated in the positive sera by immunodiffusion techniques. Rabbits appear to be good PCA recipients for determination and titration of canine reaginic antibodies.

Production and properties of reaginic antibodies in rabbits infected with Clonorchis sinensis or Schistosoma japonicum

The production of reaginic antibodies detected by homologous passive cutaneous anaphylaxis (PCA) was demonstrated in all rabbits experimentally infected with either Clonorchis sinensis or Schistosoma japonicum. The antibodies appeared in the sera as early as 3 weeks after exposure and persisted with relatively high titers for at least 7 weeks in some animals. The antisera of rabbits infected with C. sinensis were found to be cross reactive against heterologous trematode antigens, although PCA titers were less than 3% of the titer by the homologous antigen; no cross reaction was observed between S. japonicum antiserum and the heterologous antigens. PCA activity of the antisera was completely destroyed in some samples by heat treatment at 56 C for 2 hr, but partially in the others even after heating for 6 hr. However, the physicochemical properties of these antibodies were analogous to human IgE; the PCA activity was eluted with 0.035 M phosphate buffer from a DEAE-cellulose column and recovered in the ascending portion of the IgG peak by Sephadex G-200 gel filtration. PCA activity was found in a β region in preparative agar electrophoresis.

Competitive Effect of Homologous IgG or Fc in Sensitization of Rabbits for PCA Mediated by Reaginic Antibody

Abstract Rabbit IgG or their Fc fragment inhibit sensitization for homologous passive cutaneous anaphylaxis by rabbit IgE. Fab fragment from rabbit IgG had no inhibitory effect.

The apparent inability of cyprinid fish to produce skin‐sensitizing antibody

Both egg albumin and horse serum failed to induce systemic anaphylactic shock in cyprinid fish. The production of skin‐sensitizing antibody by these fish to either horse serum, egg albumin or antigenic extracts of the cestode, Caryophyllaeus laticeps or the acantho‐cephalan, Pomphorhynchus laevis, could not be demonstrated by homologous passive cutaneous anaphylaxis (PCA) or by heterologous PCA reaction in guinea‐pigs. It was considered therefore, that fish are unable to produce such antibody, at least in response to these antigens, and that it is unlikely that skin‐sensitizing antibody is involved in the rejection of C. laticeps by dace Leuciscus lueciscus (L.). The phylogenetic origins of skin‐sensitizing antibody are discussed.

Homocytotropic Antibody in Primary Responder and Hyperimmune Rabbits

Abstract Homocytotropic antibody against ovalbumin was found in both the primary and secondary responses in the rabbit. A comparison was made between HCA from the primary response and that from the hyperimmune response. No significant difference was found between the two using these criteria of comparison: percentage of animals responding, molecular size, electrophoretic mobility, heat and mercaptoethanol sensitivity, latent period required and maternal transfer of the activity. It appears that the same IgE-like antibody which elicits homologous passive cutaneous anaphylaxis reactions can be present in rabbits after one injection of ovalbumin or after a series of injections.