Madara J L, Patapoff T W, Gillece-Castro B, Colgan S P, Parkos C A, Delp C, Mrsny R J
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
J Clin Invest. 1993 May;91(5):2320-5. doi: 10.1172/JCI116462.
Neutrophil transmigration across intestinal epithelia is thought to contribute to epithelial dysfunction and characterizes many inflammatory intestinal diseases. Neutrophils activated by factors, normally present in the lumen, release a neutrophil-derived secretagogue activity to which intestinal epithelia respond with an electrogenic chloride secretion, the transport event which underlies secretory diarrhea. Using sequential ultrafiltration, column chromatographic, and mass and Raman spectroscopic techniques, neutrophil-derived secretagogue was identified as 5'-AMP. Additional studies suggested that neutrophil-derived 5'-AMP is subsequently converted to adenosine at the epithelial cell surface by ecto-5'-nucleotidase and that adenosine subsequently activates intestinal secretion through adenosine receptors on the apical membrane of target intestinal epithelial cells. These findings suggest that this ATP metabolite may serve as a neutrophil-derived paracrine mediator that contributes to secretory diarrhea in states of intestinal inflammation.
中性粒细胞穿越肠上皮的迁移被认为会导致上皮功能障碍,并是许多炎症性肠病的特征。通常存在于肠腔内的因子激活中性粒细胞后,会释放一种源自中性粒细胞的促分泌活性物质,肠上皮对此的反应是产生电致氯化物分泌,这一转运过程是分泌性腹泻的基础。通过连续超滤、柱色谱以及质谱和拉曼光谱技术,源自中性粒细胞的促分泌物质被鉴定为5'-AMP。进一步的研究表明,源自中性粒细胞的5'-AMP随后在上皮细胞表面被ecto-5'-核苷酸酶转化为腺苷,而腺苷随后通过靶肠上皮细胞顶端膜上的腺苷受体激活肠道分泌。这些发现表明,这种ATP代谢产物可能作为一种源自中性粒细胞的旁分泌介质,在肠道炎症状态下导致分泌性腹泻。