Madara J L, Carlson S
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
J Clin Invest. 1991 Feb;87(2):454-62. doi: 10.1172/JCI115017.
We have previously shown that Na(+)-coupled transport of glucose and amino acids across the apical membrane of intestinal absorptive cells is accompanied by alterations in cytoskeletal structure and altered sieving of small hydrophilic solutes by tight junctions. Here we report that in response to the essential amino acid L-tryptophan at lumenal concentrations likely to be supraphysiological (1 mM or greater), these responses are so exaggerated as to induce disruption of tight junctions and transepithelial macromolecular leaks. Since these effects of L-tryptophan are energy and Na+ dependent and occur with mucosal but not serosal exposure to L-tryptophan, it appears they are triggered by activation of a Na(+)-nutrient cotransporter in the apical membrane of absorptive cells rather than by the presence of an unidentified trace contaminant. Our findings suggest the possibility that dietary supplementation by L-tryptophan may result in loss of the intestinal epithelial barrier to dietary antigens. We speculate that such a response to supraphysiologic tryptophan may contribute, in part, to the recently recognized curious tryptophan-induced eosinophilia myalgia syndrome.
我们之前已经表明，钠耦联的葡萄糖和氨基酸跨肠吸收细胞顶端膜的转运伴随着细胞骨架结构的改变以及紧密连接对小的亲水性溶质筛分作用的改变。在此我们报告，在肠腔浓度可能超出生理水平（1 mM或更高）的必需氨基酸L-色氨酸作用下，这些反应会被极大地放大，从而导致紧密连接的破坏和跨上皮大分子渗漏。由于L-色氨酸的这些效应依赖能量和钠离子，且在黏膜而非浆膜接触L-色氨酸时出现，所以它们似乎是由吸收细胞顶端膜上的钠-营养共转运体的激活引发的，而非由一种未鉴定的微量污染物导致。我们的发现提示了L-色氨酸膳食补充可能导致肠道上皮对膳食抗原屏障丧失的可能性。我们推测，对超生理水平色氨酸的这种反应可能部分促成了最近认识到的奇怪的色氨酸诱导的嗜酸性粒细胞增多性肌痛综合征。
