Specific Antibody Responses to Subtilisin Carlsberg (Alcalase) in Mice: Development of an Intranasal Exposure Model

Robinson, Michael K.; Babcock, Laura S.; Horn, Patricia A.; Kawabata, Thomas T.

doi:10.1093/toxsci/34.1.15

Cited by 11 publications

(14 citation statements)

References 39 publications

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“…Although IgE antibody is accepted as the major mediator of immediate hypersensitivity allergic reactions in humans, in mice a subclass of IgG (IgG1) can also sensitize mast cells and trigger anaphylaxis (Silva et al, 2008). The IgG1 subclass is subject to similar immune regulation as is IgE and is therefore used as a surrogate marker for IgE antibody responses (Birmingham et al, 2002;Robinson et al, 1996). In contrast, IgG2a antibody production displays a reciprocal relationship with IgE and IgG1 antibody responses (Stevens et al, 1988;Zakroff et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the allergenic potential of proteins: an assessment of the kiwifruit allergen actinidin

Dearman

Beresford

Foster

et al. 2013

J of Applied Toxicology

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Assessment of the potential allergenicity (IgE-inducing properties) of novel proteins is an important challenge in the overall safety assessment of foods. Resistance to digestion with pepsin is commonly measured to characterize allergenicity, although the association is not absolute. We have previously shown that specific IgE antibody production induced by systemic [intraperitoneal (i.p.)] exposure of BALB/c strain mice to a range of proteins correlates with allergenic potential for known allergens. The purpose of the present study was to explore further the utility of these approaches using the food allergen, actinidin. Recently, kiwifruit has become an important allergenic foodstuff, coincident with its increased consumption, particularly as a weaning food. The ability of the kiwifruit allergen actinidin to stimulate antibody responses has been compared with the reference allergen ovalbumin, and with the non-allergen bovine haemoglobin. Haemoglobin was rapidly digested by pepsin whereas actinidin was resistant unless subjected to prior chemical reduction (reflecting intracellular digestion conditions). Haemoglobin stimulated detectable IgG antibody production at relatively high doses (10%), but failed to provoke detectable IgE. In contrast, actinidin was both immunogenic and allergenic at relatively low doses (0.25% to 1%). Vigorous IgG and IgG1 antibody and high titre IgE antibody responses were recorded, similar to those provoked by ovalbumin. Thus, actinidin displays a marked ability to provoke IgE, consistent with allergenic potential. These data provide further encouragement that in tandem with analysis of pepsin stability, the induction of IgE after systemic exposure of BALB/c strain mice provides a useful approach for the prospective identification of protein allergens.

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Section: Discussionmentioning

confidence: 99%

Characterization of the allergenic potential of proteins: an assessment of the kiwifruit allergen actinidin

Dearman

Beresford

Foster

et al. 2013

J of Applied Toxicology

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“…BALB/c (H‐2d), CBA/J (H‐2k), and C57BL/6 (H‐2b) were high, moderate, and low responders, respectively, in terms of IgE responsiveness to SEA. It is known that Ab production is genetically restricted, especially with MHC class II antigen, in experimental models with intranasal administration of antigens as well as systemic immunization (9, 16, 27, 28). Tamura et al showed that BDF1 (H‐2b/d), BALB/c, and C3H (H‐2k) were high, intermediate, and low responders with respect to ovalbumin (OVA) by intranasal immunization of OVA together with the cholera toxin B subunit (9).…”

Section: Discussionmentioning

confidence: 99%

“…Tamura et al showed that BDF1 (H‐2b/d), BALB/c, and C3H (H‐2k) were high, intermediate, and low responders with respect to ovalbumin (OVA) by intranasal immunization of OVA together with the cholera toxin B subunit (9). On the other hand, Robinson et al demonstrated that the H‐2b haplotype is positively associated with IgG1 production in intranasal immunization with alcalase together with the detergent matrix (27). We also demonstrated that CBA/J mice (H‐2k) responded well with IgE production after intranasal sensitization with phospholipase A 2 from bee venom, whereas C57BL/6 mice (H‐2b) responded poorly (in press).…”

Section: Discussionmentioning

confidence: 99%

Strain‐dependent induction of allergic rhinitis without adjuvant in mice

Okano

Harn

Abe

et al. 1999

Allergy

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“…IgG1 is co‐regulated with IgE in the mouse via the Th2/IL‐4 pathway (Purkerson & Isakson 1992). Thus, Robinson et al (1996) stated that IgG1 formation is a highly practical and robust marker for the assessment of the relative allergenicity of enzymes and other proteins. In mice, the IgG1 response may therefore be used as an indicator, in addition to the IgE response, for the evaluation of hazard for the development of Type I allergy in humans.…”

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confidence: 99%

Adjuvant Effect of di‐n‐Butyl‐, di‐n‐Octyl‐, di‐iso‐Nonyl‐ and di‐iso‐Decyl Phthalate in a Subcutaneous Injection Model Using BALB/c Mice

Larsen

Lund

Nielsen

et al. 2002

Pharmacology & Toxicology

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During the last decades, the prevalence of the allergic airway diseases, asthma and rhinitis, has increased worldwide. Introduction of environmental chemicals with adjuvant effect may play a role in this increase. In the present study, the adjuvant effects of di-n-butyl-, di-n-octyl-, di-iso-nonyl-and di-iso-decyl phthalate are studied in a screening model. Ovalbumin, used as the model antigen, was injected subcutaneously in the neck region of BALB/cJ mice with the selected phthalate in concentrations from 2-2000 mg/ml. Additionally, the mice were boosted once or twice with ovalbumin alone. Immunization with ovalbumin alone, the ovalbumin control group, served as the baseline for antibody production, whereas aluminium hydroxide served as the positive control. The levels of ovalbumin-specific IgE, IgG1 and IgG2a antibodies in sera were determined. Adjuvant effect was accepted to be present if a statistical increase in antibody production occurred in a test group as compared to an ovalbumin control group together with the fulfillment of dose-response relationships. Adjuvant effect varied strongly between the phthalates investigated. Phthalates with 8 or 9 carbon atoms in the alkyl side chains were the stronger adjuvants whereas phthalates with shorter or longer alkyl side chains possessed less adjuvant activity. Adjuvant effects were apparent either from the IgE or the IgG1 response or both, whereas no effect was seen on the IgG2a response. Additional studies with airborne exposure are required to establish whether the hazards also result in a significant risk for the development of allergy in man.

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Specific Antibody Responses to Subtilisin Carlsberg (Alcalase) in Mice: Development of an Intranasal Exposure Model

Cited by 11 publications

References 39 publications

Characterization of the allergenic potential of proteins: an assessment of the kiwifruit allergen actinidin

Characterization of the allergenic potential of proteins: an assessment of the kiwifruit allergen actinidin

Strain‐dependent induction of allergic rhinitis without adjuvant in mice

Adjuvant Effect of di‐n‐Butyl‐, di‐n‐Octyl‐, di‐iso‐Nonyl‐ and di‐iso‐Decyl Phthalate in a Subcutaneous Injection Model Using BALB/c Mice

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