Coenzyme A contained in mothers' milk is associated with the potential to induce atopic dermatitis
Coenzyme A contained in mothers' milk is associated with the potential to induce atopic dermatitis
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DOI：
10.1093/intimm/dxr085
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发表时间：
2011-12-01
影响因子：
4.4
通讯作者：
Matsushita, Sho
中科院分区：
文献类型：
--
作者：
Higashi, Takehiro;Shimojo, Naoki;Matsushita, Sho
使用体外培养的人树突状细胞，通过混合淋巴细胞反应和细胞内环腺苷3‘，5’-单磷酸浓度的变化，可以定性和定量地评价T(H)2佐剂活性。目前的研究表明，母亲的孩子(n=55)在出生后6个月内患上特应性皮炎(AD)，与那些孩子没有出现这种症状的母亲相比，她们的牛奶中通常表现出更高的T(H)2佐剂活性。这样的活性在母乳的液态中被恢复，并被反相高效液相洗脱为单一组分。对这一组分的进一步质谱分析表明，来自分子量为767.53的因子的信号被观察到，仅在具有高T(H)2佐剂活性的牛奶中观察到。实际上，低浓度的辅酶A在体外和体内都表现出T(H)2佐剂活性。此外，口服辅酶A后，小鼠肠系膜淋巴非T细胞可诱导同种异体幼稚的CD4(+)T细胞分化为T(H)2。此外，口服辅酶A可引起小鼠皮肤粗糙、表皮增生、棘层颗粒增多、层增厚。这些数据共同表明，一些AD患者在出生后立即接触到含有高T(H)2佐剂活性的母乳，这可能是由于牛奶中含有辅酶A。
T(h)2 adjuvant activity can be qualitatively and quantitatively evaluated using a mixed lymphocyte reaction and by changes in the intracellular cyclic adenosine 3',5'-monophosphate concentration, using human dendritic cells in vitro. The current study shows that mothers, whose children (n = 55) developed atopic dermatitis (AD) within 6 months after birth, often demonstrate a higher T(h)2 adjuvant activity in their milk, in comparison to those whose children did not develop such symptoms. Such an activity was recovered in a liquid phase of mothers' milk and was eluted as a single fraction by reversed-phase HPLC. Further analysis of this fraction by mass spectrometry showed that signals originating from a factor with a molecular weight of 767.53 are observed, exclusively in milk with a high T(h)2 adjuvant activity. The mass is exactly that of Coenzyme A (CoA), and indeed, a low concentration of CoA exhibited T(h)2 adjuvant activity both in vitro and in vivo. Moreover, mesenteric lymph node non-T cells obtained from mice that were orally treated with CoA led allogeneic naive CD4(+) T cells to differentiate into T(h)2. Furthermore, the oral administration of CoA induced rough skin, hyperplasia of the epidermis, hypergranulosis in the spinous layer and the thickening of the stratum in mice. These data collectively indicate that some of the patients with AD were exposed to mothers' milk carrying high T(h)2 adjuvant activity right after birth, which may be attributable to presence of CoA contained in the milk.