期刊
ALLERGY
卷 63, 期 7, 页码 882-890出版社
WILEY
DOI: 10.1111/j.1398-9995.2008.01673.x
关键词
anaphylaxis; antigen uptake; milk allergy; oral sensitization; Peyer's patches
资金
- Austrian Science Fund FWF [J 2614] Funding Source: Medline
- NCI NIH HHS [5R24 CA095823-04] Funding Source: Medline
- NCRR NIH HHS [1 S10 RR0 9145-01] Funding Source: Medline
- NIAID NIH HHS [AI23504, AI45343, AI44236, AI61093] Funding Source: Medline
- NIDDK NIH HHS [DK72201] Funding Source: Medline
Background: The underlying mechanisms responsible for allergic sensitization to food proteins remain elusive. To investigate the intrinsic properties (as well as the effect of pasteurization) of the milk proteins alpha-lactalbumin, beta-lactoglobulin and casein that promote the induction of milk allergy. Methods: Alteration of structure and immune-reactivity of native and pasteurized proteins was assessed by gel filtration and ELISA. Uptake of these proteins was compared in vitro and in vivo. The biological effect was assessed by orally sensitizing C3H/HeJ mice with milk proteins followed by a graded oral challenge. Required dose to induce anaphylaxis, symptoms and mean body temperature was recorded. Antigen-specific antibodies and cytokine production by splenocytes were analyzed. Results: Soluble beta-lactoglobulin and alpha-lactalbumin but not insoluble casein were readily transcytosed through enterocytes in vitro and in vivo. Pasteurization caused aggregation of beta-lactoglobulin and alpha-lactalbumin inhibiting uptake by intestinal epithelial cells in vitro and in vivo. Furthermore, aggregation redirected uptake to Peyer's patches, which promoted significantly higher Th2-associated antibody and cytokine production in mice than their native counterparts. Despite this only the soluble forms of beta-lactoglobulin and alpha-lactalbumin elicited anaphylaxis (following priming) when allergens were administered orally. Aggregated beta-lactoglobulin and alpha-lactalbumin as well as casein required systemic administration to induce anaphylaxis. Conclusions: These results indicate that triggering of an anaphylactic response requires two phases (1) sensitization by aggregates through Peyer's patches and (2) efficient transfer of soluble protein across the epithelial barrier. As the majority of common food allergens tend to form aggregates, this may be of clinical importance.
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