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Physical Fitness Test Found in the Spleen

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What’s a spleen good for? Is it just something to vent when angry? No, it’s an organ under the rib cage that can be removed surgically in extreme circumstances. But you should hang onto yours as long as you can. Located just left of the stomach, the spleen serves several functions: filtering blood, recycling old blood cells, fighting certain kinds of bacteria, and storing parts of the immune system including white blood cells and platelets.

Now, a new function discovered at MIT bears the hallmarks of intelligent design. It has tissues that impose a “physical fitness test” on red blood cells (RBCs). According to news from MIT:

Red blood cells must be small and flexible enough to squeeze through the tiniest capillaries of the body, where they deliver oxygen to surrounding cells. In the late 1960s, scientists proposed that the minute dimensions of these capillaries, which are less than 4 micrometers in diameter, are responsible for defining the size and shape of red blood cells.

However, a new study led by MIT researchers reveals that these blood cell traits are actually determined by the smallest opening in the spleen. This narrow passage, known as the interendothelial slit, imposes a more stringent “physical fitness test” that all blood cells must pass before continuing to circulate through the body. [Emphasis added.]

Like recruits for the army, the cells have to match up before being allowed into service. But unlike the army, recruits who fail are eaten and recycled! This is how the body makes sure RBCs will make it through narrow capillaries in all the remote parts of the body — an easier fitness test for them. The spleen, in effect, overtrains the RBCs, making sure they can endure whatever challenges they will face ahead when some of them must pass through the narrowest of capillaries.

What’s really neat about this interendothelial slit (IES) is that it calibrates RBCs in three dimensions: height, width, and depth. Look at the figures in the open-access paper in Proceedings of the National Academy of Sciences. The first figure shows RBCs arriving at the IES by two routes: through the splenic artery or through “red pulp.” Either way, they have to face the slits in the IES as pressure forces them forward. The slits in this epithelial tissue are precisely spaced to force an RBC to try to squeeze through. Diseased cells or spherical cells are likely to fail the test; if they do, they will be recycled at the hands of macrophages or dendritic cells. Those that pass proceed into the splenic vein to be sent into service throughout the body.

In the figures, the slits look like stiff gates. The drawings are actually mathematical models of the process, which cannot be dynamically observed in living humans.

The spleen’s primary function is to remove old red blood cells from circulation when they can no longer perform their job. To explore how much of a role the spleen plays in determining the size and shape of red blood cells, the researchers developed a computer simulation to model how these cells squeeze through tiny slits formed by the spaces between the endothelial cells lining the spleen’s blood vessels. As blood flows through the spleen, about 10 percent of the red blood cells are diverted through these slits, which have maximum dimensions of 1.2 micrometers in height (about 1/80 the thickness of a human hair), 4 micrometers in width, and 1.9 micrometers in depth. This slit is more likely to stop old or spherical red blood cells, while a long circular tube such as a capillary may allow them to go through.

As anyone knows who has watched surgical movies, though, internal organs are soft, squishy and bloody. Can a squishy organ actually operate a physical fitness test where size matters?

Evidence suggests that the model reflects reality. For one thing, it’s more than a computer simulation. It’s built on “a variety of experimental observations,” including knowledge of pathological conditions where the spleen becomes a circulatory bottleneck, causing a variety of acute and chronic conditions. Additionally, RBCs that exit a healthy spleen have a more consistent ratio between volume and diameter than those who skip the test. There’s more evidence from medical practice, too.

The findings are consistent with some other evidence that the spleen determines red blood cell shape and size. Some patients with a disorder called spherocytosis, in which red blood cells are round instead of disc-shaped, are treated by having their spleens removed. These patients’ red blood cells take on a larger range of sizes, suggesting that the spleen was limiting the size of the cells. The findings are also consistent with previous experiments on isolated human spleens perfused with healthy red blood cells, removed from patients with benign tumors of the pancreas.

The authors imagine how the spleen could help filter RBCs infected with malaria. Drugs might be manufactured that make infected cells too large or too stiff to fit through the filter. These would be blocked by the spleen and broken down.

Figure 2 shows how the IES puts the squeeze on red blood cells. They have to do a kind of “limbo” to get through the slit, bending tightly, passing through, then popping out to full size on the other side. This would be like getting through “Fat Man’s Misery” in some tour caves.

The authors describe how this new knowledge could lead to the development of synthetic spleens to help filter blood for those with splenectomies. In fact, experiments have been done with microsphere filters matching the dimensions of the spleen IES, with comparable pressure gradients, and the results on RBCs passing through the “physical fitness test” are comparable.

These experimental results directly verify the mechanical sensing of RBCs by the human spleen. The results further suggest that the microsphere filter provides a mechanically equivalent system to the human spleen, by recourse to which controlled experiments could be performed to quantify the mechanics of the spleen in a manner that is not possible in the human spleen. Such experiments reveal that retention of abnormal RBCs is based mainly on their mechanical properties even without any ligand-receptor interactions between RBCs and splenic structures.

Any defect in the RBC or the IES is likely to cause life-threatening conditions. Sickle-cell disease, malaria, genetic disorders and some blood cancers can lead to various kinds of anemia as RBCs pile up in the spleen, unable to get through the slits. In healthy people, though, the spleen “contributes to the quality assurance of circulating RBCs,” they conclude. “Our approach forms the first step of a potential systematic reconstruction of the navigation of RBCs in the human spleen across narrow slits but also upstream and downstream from this unique circulatory bottleneck.

Finding a new function for a well-known human organ is pretty exciting. It’s even more exciting to find additional evidence of irreducible complexity and intelligent design at work. Think of it — the organ that produces RBCs (bone marrow) faces an independent “quality assurance” mechanism in a separate organ, the spleen. The cells of the IES cannot see RBCs, yet they organize into precision slits that are just the right size and shape to test their “physical fitness.” They do this by calibrating RBC size and flexibility using “mechanical properties” to ensure they can endure challenges in distant parts of the body. Both the slit sizes and pressures driving RBCs through the slits must be just right. To top all these wonders, consider that all these systems are ultimately encoded in DNA and put into place during embryonic development.

How could any of this arrive by unguided processes that accumulate selected mistakes? That makes no sense. The one cause we know can organize multiple parts to test concordance with requirements is intelligence. The spleen’s obstacle course and physical fitness test arouses a sense of familiarity in all of us who know about basic training in the military and quality assurance testing in industry.

Feel your lower left ribs and be thankful for that spleen under there. Along with many, many other organs in the body, it helps maintain system requirements to keep your multi-level operation humming.

Photo credit: DoD/Staff Sgt. Charles Crail, U.S. Army [Public domain], via Wikimedia Commons.

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