Graphical summary. Credit: Immunity (2023). DOI: 10.1016/j.immuni.2023.12.003
Researchers from Zhejiang University School of Medicine, China, studied how the innate immune system of kidney macrophages works to prevent kidney stones. In an article titled “Kidney Macrophages Monitor and Remove Particles from Urine to Prevent Tubule Blockage,” published in ImmunityThe authors detail their findings on the mechanistic actions and strategic positioning of macrophages to monitor epithelial cells and intratubular environments.
As urine passes through the tubular system of the kidneys, it generates various microscopic sediment particles, including mineral crystals, from the concentrated urine. Pathological conditions can result in the presence of inflammatory proteins and cells. These particles can lodge in the tubules, blocking urine flow and causing kidney dysfunction.
The researchers observed kidney macrophages adjacent to the tubules in real time, using high-resolution microscopy, live recordings and two-photon microscopy techniques. They were able to record macrophages extending transepithelial protrusions and interacting with intratubular particles, as well as their migration to facilitate excretion of urine particles.
These techniques captured the association of macrophages with particles present in urine and demonstrated the role of macrophages in particle clearance. Renal macrophages located near the medullary tubules exhibit specific behaviors, extending transepithelial protrusions and constantly sampling urine contents.
Macrophages were then observed to migrate and surround the intratubular particles, thus facilitating their elimination from the tubular system. Mice were injected with fluorescent inert latex beads into the kidney, and after 12 hours, free beads were almost absent from the lumen of the collecting ducts.
To confirm the role of macrophages, the latex bead experiment was repeated on mice lacking renal macrophages. Macrophage-depleted mice showed increased retention of fluorescent beads even after 36 hours despite the more prolonged exposure to natural urine flushing.
This result suggests that normal urine flushing alone could not effectively remove large particles in the renal tubular system without the prior elimination assistance of macrophages.
The results suggest potential therapeutic implications for kidney stones (nephrolithiasis or kidney stones) and for the development of kidney-specific drug delivery methods based on these distinctive macrophage characteristics.
More information:
Jian He et al, Renal macrophages monitor and remove particles from urine to prevent tubule obstruction, Immunity (2023). DOI: 10.1016/j.immuni.2023.12.003
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