Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Immunity. 2024 Jan 9;57(1):106-123.e7. doi: 10.1016/j.immuni.2023.12.003. Epub 2023 Dec 29.
When the filtrate of the glomerulus flows through the renal tubular system, various microscopic sediment particles, including mineral crystals, are generated. Dislodging these particles is critical to ensuring the free flow of filtrate, whereas failure to remove them will result in kidney stone formation and obstruction. However, the underlying mechanism for the clearance is unclear. Here, using high-resolution microscopy, we found that the juxtatubular macrophages in the renal medulla constitutively formed transepithelial protrusions and "sampled" urine contents. They efficiently sequestered and phagocytosed intraluminal sediment particles and occasionally transmigrated to the tubule lumen to escort the excretion of urine particles. Mice with decreased renal macrophage numbers were prone to developing various intratubular sediments, including kidney stones. Mechanistically, the transepithelial behaviors of medulla macrophages required integrin β1-mediated ligation to the tubular epithelium. These findings indicate that medulla macrophages sample urine content and remove intratubular particles to keep the tubular system unobstructed.
当肾小球的滤液流经肾小管系统时,会产生各种微观的沉淀物颗粒,包括矿物晶体。排除这些颗粒对于确保滤液的自由流动至关重要,否则将导致肾结石形成和阻塞。然而,其清除的潜在机制尚不清楚。在这里,我们使用高分辨率显微镜发现,肾髓质中的近曲小管巨噬细胞持续形成跨上皮突起并“采样”尿液内容物。它们有效地隔离和吞噬管腔内的沉淀物颗粒,偶尔也会迁移到肾小管腔中,护送尿颗粒的排泄。巨噬细胞数量减少的小鼠更容易发生各种管腔内沉淀物,包括肾结石。从机制上讲,近曲小管巨噬细胞的跨上皮行为需要整合素 β1 介导的与管状上皮的连接。这些发现表明,髓质巨噬细胞“采样”尿液内容物并清除管腔内颗粒,以保持管状系统通畅。