Roth-Walter F, Berin M C, Arnaboldi P, Escalante C R, Dahan S, Rauch J, Jensen-Jarolim E, Mayer L
Center of Immunobiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Allergy. 2008 Jul;63(7):882-90. doi: 10.1111/j.1398-9995.2008.01673.x.
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.
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.
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.
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.
食物蛋白过敏致敏的潜在机制仍不清楚。为了研究乳蛋白α-乳白蛋白、β-乳球蛋白和酪蛋白促进牛奶过敏诱导的内在特性（以及巴氏杀菌的影响）。
通过凝胶过滤和酶联免疫吸附测定评估天然和巴氏杀菌蛋白的结构改变和免疫反应性。在体外和体内比较这些蛋白的摄取情况。通过用乳蛋白口服致敏C3H/HeJ小鼠，随后进行分级口服激发来评估生物学效应。记录诱导过敏反应所需的剂量、症状和平均体温。分析脾细胞产生的抗原特异性抗体和细胞因子。
可溶性β-乳球蛋白和α-乳白蛋白而非不溶性酪蛋白在体外和体内易于通过肠细胞转胞吞。巴氏杀菌导致β-乳球蛋白和α-乳白蛋白聚集，在体外和体内抑制肠道上皮细胞的摄取。此外，聚集使摄取重新导向派尔集合淋巴结，这比天然对应物在小鼠中显著促进更高的Th2相关抗体和细胞因子产生。尽管如此，当口服给予过敏原时，只有β-乳球蛋白和α-乳白蛋白的可溶性形式引发过敏反应（致敏后）。聚集的β-乳球蛋白和α-乳白蛋白以及酪蛋白需要全身给药来诱导过敏反应。
这些结果表明，过敏反应的触发需要两个阶段：（1）通过派尔集合淋巴结的聚集物致敏；（2）可溶性蛋白有效穿过上皮屏障。由于大多数常见食物过敏原倾向于形成聚集体，这可能具有临床重要性。
