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Abstract: SA-PO1045

Renal Medullary Macrophages Play a Pivotal Role in Cleaning off Intratubular Particles

Session Information

Category: Pathology and Lab Medicine

  • 1800 Pathology and Lab Medicine


  • Shen, Xiao, Zhejiang University, Hangzhou, Zhejiang, China
  • He, Jian, Zhejiang University, Hangzhou, Zhejiang, China
  • Shi, Peng, Zhejiang University, Hangzhou, Zhejiang, China

During the passage of the glomerulus filtrates through the renal tubular system, various microscopic sediment particles, including mineral crystals resulting from urine concentration, are generated. Dislodging these particles in the intratubular compartment is critical to ensure free flow of filtrate and the final formation of urine. However, the underlying cellular mechanism for the clearance is unclear.


The interactions of macrophages and segments of renal tubules were analyzed by high-resolution confocal microscopy and scanning electron microscopy. Live movement of renal macrophages was monitored by two-photon microscopy. Bulk RNA-seq was performed to analyze the transcriptomic difference between cortical and medullary macrophages. Hyperoxaluria model was used to induce kidney stone formation.


We uncovered that the juxtatubular macrophages in the renal medulla constitutively formed transepithelial protrusions and were “sampling” urine contents. This transepithelial protrusions were formed in a transcellular route instead of between epithelial cells, so that the overall junctional architecture of tubular epithelium was intact. In particular, juxtatubular macrophages were efficient in sequestering and phagocytosing intraluminal particles, and occasionally making transmigration to the tubule lumen to "escort" the excretion of sediment particles. As such, mice with underrepresentation of renal macrophages were prone to developing various intratubular sediments. Mechanistically, integrin β1-mediated ligation to the tubular epithelium is crucial to the transepithelial behaviors of medullary macrophages.


This study unveils a previously unappreciated role of renal macrophages in keeping the tubular system unobstructed. In contrast to the traditional view that the renal epithelial barrier is insurmountable to cells, we found that these juxtatubular macrophages in the medulla constitutively formed transepithelial protrusions, and the underlying molecular mechanisms were provided as well. In addition, we demonstrated a divergence between medullary and cortical macrophages in transcriptomes and in behaviors. These findings may pave way for developing novel therapeutics for nephrolithiasis as well as renal infection caused by ascending microbes.


  • Government Support – Non-U.S.