Chylomicrons promote intestinal absorption and systemic dissemination of dietary antigen (ovalbumin) in mice.

Chylomicrons promote intestinal absorption and systemic dissemination of dietary antigen (ovalbumin) in mice.
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DOI:
10.1371/journal.pone.0008442
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发表时间:
2009-12-24
期刊:
影响因子:
3.7
通讯作者:
Eckhardt E
Eckhardt E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang Y;Ghoshal S;Ward M;de Villiers W;Woodward J;Eckhardt E

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一小部分膳食蛋白质在酶降解后存活下来,并以潜在的抗原形式被吸收。这可以引发乳糜泻或食物过敏患者的炎症反应,但通常会诱导全身免疫耐受(口服耐受)。目前尚不清楚饮食抗原是如何被吸收的。大多数斯台普斯,包括具有共同抗原的主食,如花生、鸡蛋和牛奶,都含有长链甘油三酯(LCT),可刺激肠系膜淋巴流量和乳糜微粒通过肠系膜淋巴结(MLN)和血液的餐后转运。大多数饮食抗原,如卵清蛋白(OVA),是乳化剂,预测乳糜微粒的亲和力。我们推测乳糜微粒的形成促进了食物抗原的肠道吸收和全身传播。与不刺激乳糜微粒形成的中链甘油三酯(MCT)相比,当将OVA与LCT一起灌胃至禁食小鼠时,MLN和血液中的OVA吸收显著增强。LCT的作用被乳糜微粒分泌抑制剂Pluronic L-81阻断。当用LCT灌胃OVA时,连续转移的OVA特异性DO11.10 T细胞在外周淋巴结中的增殖比用MCT或LCT加Pluronic L-81时更广泛,表明饮食中的OVA是全身性播散的。血浆中的大多数膳食OVA与乳糜微粒相关,表明这些颗粒介导全身抗原传播。肠上皮CaCo-2细胞分泌更多的细胞相关的,外源性的OVA时,刺激与油酸比丁酸,分泌的OVA似乎与乳糜微粒。餐后乳糜微粒的形成深刻地影响饮食抗原的吸收和全身传播。膳食中的脂肪含量可通过调节抗原吸收和转运来影响对膳食抗原的免疫应答。
A small fraction of dietary protein survives enzymatic degradation and is absorbed in potentially antigenic form. This can trigger inflammatory responses in patients with celiac disease or food allergies, but typically induces systemic immunological tolerance (oral tolerance). At present it is not clear how dietary antigens are absorbed. Most food staples, including those with common antigens such as peanuts, eggs, and milk, contain long-chain triglycerides (LCT), which stimulate mesenteric lymph flux and postprandial transport of chylomicrons through mesenteric lymph nodes (MLN) and blood. Most dietary antigens, like ovalbumin (OVA), are emulsifiers, predicting affinity for chylomicrons. We hypothesized that chylomicron formation promotes intestinal absorption and systemic dissemination of dietary antigens. Absorption of OVA into MLN and blood was significantly enhanced when OVA was gavaged into fasted mice together with LCT compared with medium-chain triglycerides (MCT), which do not stimulate chylomicron formation. The effect of LCT was blocked by the addition of an inhibitor of chylomicron secretion, Pluronic L-81. Adoptively transferred OVA-specific DO11.10 T-cells proliferated more extensively in peripheral lymph nodes when OVA was gavaged with LCT than with MCT or LCT plus Pluronic L-81, suggesting that dietary OVA is systemically disseminated. Most dietary OVA in plasma was associated with chylomicrons, suggesting that these particles mediate systemic antigen dissemination. Intestinal-epithelial CaCo-2 cells secreted more cell-associated, exogenous OVA when stimulated with oleic-acid than with butyric acid, and the secreted OVA appeared to be associated with chylomicrons. Postprandial chylomicron formation profoundly affects absorption and systemic dissemination of dietary antigens. The fat content of a meal may affect immune responses to dietary antigens by modulating antigen absorption and transport.
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