Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid
Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid
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DOI：
10.1073/pnas.2131556100
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发表时间：
2003-10-14
影响因子：
11.1
通讯作者：
Muchmore, E
中科院分区：
文献类型：
--
作者：
Tangvoranuntakul, P;Gagneux, P;Muchmore, E
人类由于在与类人猿的最后共同祖先之后发生的一种突变，在基因上无法产生唾液酸N - 羟乙酰神经氨酸（Neu5Gc）。尽管正常人类中被假定不存在Neu5Gc，但据称在人类肿瘤和胎儿胎粪中存在少量该物质。我们已经研制出一种对Neu5Gc具有高度特异性和亲和力的抗体。人类的胎儿组织、正常成人组织以及乳腺癌组织对这种抗体有反应，主要是在分泌上皮和血管内。通过质谱分析证实了少量Neu5Gc的存在。由于其合成没有任何已知的替代途径，我们推断这些少量的Neu5Gc可能来自外源性来源。事实上，用Neu5Gc喂养的人类细胞会将其整合到内源性糖蛋白中。当正常人类志愿者摄入Neu5Gc时，一部分被吸收并通过尿液排出，少量被整合到新合成的糖蛋白中。据我们所知，植物或微生物中从未报道过Neu5Gc。我们发现Neu5Gc在家禽和鱼类中很少见，在奶制品中常见，在红肉中含量丰富。此外，正常人类体内针对Neu5Gc的循环IgA、IgM和IgG抗体数量不等，其中最高水平与先前已知的抗α - 半乳糖异种反应性抗体相当。这一发现表明，人类会吸收并代谢性地整合一种在哺乳动物源性食物中含量丰富的非人类膳食成分，同时还会产生针对同一分子的异种反应性以及潜在的自身反应性抗体。对人类疾病的潜在影响进行了简要讨论。
Humans are genetically unable to produce the sialic acid N-glycolyineuraminic acid (Neu5Gc), because of a mutation that occurred after our last common ancestor with great apes. Although Neu5Gc is presumed absent from normal humans, small amounts have been claimed to exist in human tumors and fetal meconium. We have generated an antibody with high specificity and avidity for Neu5Gc. Fetal tissues, normal adult tissues, and breast carcinomas from humans showed reactivity to this antibody, primarily within secretory epithelia and blood vessels. The presence of small amounts of Neu5Gc was confirmed by MS. Absent any known alternate pathway for its synthesis, we reasoned that these small amounts of Neu5Gc might originate from exogenous sources. indeed, human cells fed with Neu5Gc incorporated it into endogenous glycoproteins. When normal human volunteers ingested Neu5Gc, a portion was absorbed and eliminated in urine, and small quantities were incorporated into newly synthesized glycoproteins. Neu5Gc has never been reported in plants or microbes to our knowledge. We found that Neu5Gc is rare in poultry and fish, common in milk products, and enriched in red meats. Furthermore, normal humans have variable amounts of circulating IgA, IgM, and IgG antibodies against Neu5Gc, with the highest levels comparable to those of the previously known anti-alpha-galactose xenoreactive antibodies. This finding represents an instance wherein humans absorb and metabolically incorporate a nonhuman dietary component enriched in foods of mammalian origin, even while generating xenoreactive, and potentially autoreactive, antibodies against the same molecule. Potential implications for human diseases are briefly discussed.