*For medical professionals only
The first time Singularity Cake heard about kidney stones, it was when I was in high school, our kind and nagging class teacher who was comparable to Tang Seng suddenly disappeared for a few days, and the classmates mysteriously said that the old class was hospitalized with kidney stones.
It's too reasonable, just our 6 in the morning and 10 in the evening, the work intensity of the head teacher, I can't drink a few sips of water at the end of the day, and the kidney stones are very reasonable.
What to do if you go to search for kidney stones now, no matter what type of kidney stones, in addition to taking medicine and surgery, there will always be people who advise you to drink more water. Indeed, urine flushing is the main means of taking away the crystalline particles of the urinary tract, but recently, scientists from Zhejiang University have found that in fact, there is a group of conscientious "quality inspectors" in the urinary tract to monitor the safety of the urinary tract at all times, and even die in the line of duty at critical moments to take away the particles and maintain the patency of the urinary tract.
These inspectors are macrophages.
Recently, the research group of Shen Xiao and Shi Peng of Zhejiang University published a paper in the journal Immunity, and researchers have discovered a new mechanism for the removal of particulate matter in urine. It turns out that macrophages surrounding the renal medullary tubules are able to spontaneously form protrusions, penetrate epithelial cells to "sample" urine contents, and even migrate to the lumen themselves, carrying particles to be excreted in the urine. This is the first time that humans have realized that urine flushing is not the only mechanism by which the urinary tract removes particulate matter.
Diagram of the title of the dissertation
The kidneys are the body's key "filters" responsible for screening and excreting metabolic waste. The raw urine produced from the circulation is filtered through the renal tubules, and the usable nutrients and about 99% of the water are recovered, leaving a highly concentrated final urine, in which the supersaturated substances naturally form crystallization. In addition, apoptosis tubular epithelial cells also enter the urine, and different biopathological conditions will also accelerate the deposition, so it is not surprising that there are various particles in the urine.
In fact, in one study, crystallutura was present in urine samples from about 1 in 4 healthy people. Millions of tiny particles can form in the kidneys every day, but most of them are safely excreted in the urine.
Will urine flushing be the only mechanism? Researchers don't think so.
In their experiments, they found that the renal medulla is actually densely covered with abundant macrophages, and 84.1% ±5% are in physical contact with the renal tubular epithelium in space, and the morphology of these macrophages is also very strange, longer and denser than the general macrophage "tentacles", which at first glance will be mistaken for dendritic cells.
There are so many special features, it can't be ordinary macrophages.
Peritubular macrophages (green) pseudopodia are more numerous and longer
After electron microscopy and 3D modeling, we can clearly observe that these macrophages really have a special love for the renal tubules, and the protrusions formed by the macrophages are tightly wrapped around the tubules, and even some are embedded in the epithelium.
Protrusions formed by macrophages are embedded in the epithelium
If you take a closer look at the embedded part, it's even more incredible.
In general, immune cells move through the intercellular space, and researchers originally thought that macrophages stretched out their small hands from the gaps between epithelial cells, but in fact they directly penetrated the cell body of epithelial cells.
Hissing, pain for epithelial cells.
Macrophage protrusions penetrate the epithelial cell body
The researchers observed the movement of the macrophages for 2.5 hours and found that most of the cell bodies surrounding the tubular macrophages were still very stable in the epithelium, but their protruding pseudopodia were really tentative and repeated, about 5 times per hour.
What do the researchers think of it, this behavior is really sampling the contents of the tubule.
Watch the macrophages probe repeatedly
To find out what the macrophage master was doing, the researchers injected 2 μm diameter fluorescent inert latex beads into the renal pelvis injections of mice.
Two hours after injection, the beads entered the medullary collecting duct, by which time 52.4% ± 7.7% of the latex beads had been sampled by macrophage protrusions.
After 12 hours of injection, a portion of the latex beads were already transported into the macrophage cell body.
When the investigators depleted the renal macrophages in advance, the retention of latex beads in the kidney increased significantly. It seems that macrophages are really urinary tract quality inspectors, and urine flushing alone is not enough to remove particulate matter.
Macrophages extract latex beads from the urine and isolate them in their own bodies
The researchers also found that in a few cases, macrophages no longer sit firmly in the middle of the army, but migrate to the medullary collecting ducts themselves, firmly hold the captured particles into the urine, and finally escort them out of the body.
All together, tears.
Macrophages migrate to medullary collecting ducts
The macrophages that enter the collecting tube are depolarized and return to their round appearance
The researchers removed kidney macrophages from mice and supplemented them with sodium oxalate, which they found greatly accelerated the formation of kidney stones. Without the hard work of macrophage quality inspectors, the kidney area of mice was expanded by 5.8 times, and there was significant local inflammation and neutrophil infiltration.
The absence of kidney macrophages (TAM+DT) accelerates kidney stone formation
Finally, the researchers identified a key mechanism for the interaction between macrophages and renal tubular epithelial cells, integrin β1. This may be a drug target for the treatment of kidney stones in the future.
This study confirmed for the first time that urine flushing is not the only mechanism of urinary tract particulate matter removal, and the exploration of the mechanism of action of macrophages also provides a new idea for the treatment of kidney stones in the future.
Resources:
[1]https://www.cell.com/immunity/fulltext/S1074-7613(23)00534-4
The author of this article丨 Dai Siyu