Neutrophil (PMN) infiltration of the intestinal mucosa is a hallmark of gastrointestinal inflammation, with significant implications for host defense, injury and repair. However, phenotypic and mechanistic aspects of PMN recruitment in inflamed intestines have not been explored in vivo. Using novel epithelial/PMN fluorescence reporter mice, advanced intravital imaging and 3D reconstruction analysis, we mapped the microvasculature architecture across the intestinal layers and determined that in response to Salmonella/endotoxin-induced inflammation, PMN transendothelial migration (TEM) was restricted to submucosal vessels. PMN TEM was not observed in villus or crypt vessels, proximal to the epithelium that underlies the intestinal lumen, and was partially dependent on (C-X-C motif) ligands 1 (CXCL1) and 2 (CXCL2) expression, which was found to be elevated in the submucosa layer. Restricted PMN extravasation at the submucosa and subsequent PMN interstitial migration may serve as a novel regulatory step of PMN effector function and recruitment to the luminal space in inflamed intestines.

中文翻译：

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体内成像揭示了发炎肠道中独特的中性粒细胞跨内皮迁移模式。

中性粒细胞 (PMN) 浸润肠粘膜是胃肠道炎症的标志，对宿主防御、损伤和修复具有重要意义。然而，尚未在体内探索发炎肠道中 PMN 募集的表型和机制方面。使用新型上皮/PMN 荧光报告小鼠、先进的活体成像和 3D 重建分析，我们绘制了整个肠层的微血管结构，并确定响应沙门氏菌/内毒素诱导的炎症，PMN 跨内皮迁移 (TEM) 仅限于粘膜下血管. 在绒毛或隐窝血管中未观察到 PMN TEM，靠近肠腔下方的上皮细胞，并且部分依赖于（CXC 基序）配体 1（CXCL1）和 2（CXCL2）表达，发现其在粘膜下层升高。粘膜下层受限的 PMN 外渗和随后的 PMN 间质迁移可能作为 PMN 效应器功能和募集到发炎肠道管腔空间的新调节步骤。