Healthy red blood cells (RBCs) last on average for about 120 days. What happens to them at the end of their life? Researchers from the Massachusetts General Hospital led a study to find out, and discovered that the answer contradicts previously believed methods of disposal.

According to textbooks, old RBCs are eliminated by the body through the spleen using specialized macrophages that dwell in the organ. However, the researchers found that it was the liver that is the major processing site for RBC disposal and iron recycling and that there exists a transient population of recycling cells in the form of immune system cells originating from the bone marrow.

The lifespan of an RBC can be cut short when there are illnesses, such as sickle cell disease, that disrupt normal RBC production, and pathological conditions like sepsis. Cells may also be damaged during dialysis, coronary bypass surgery, or when blood transfusions are carried out and the RBCs transfused were damaged when collected, stored and administered.

When RBCs are damaged, they release iron-carrying hemoglobin in unbound forms, which can cause anemia and kidney injury, cutting back on oxygen delivery to tissues. If RBC damage associated with a disease overwhelms the body's ability to dispose of old RBCs naturally, free iron may be released into the body in toxic levels.

In the study published in the journal Nature Medicine, the researchers turned to different forms of RBC damage and investigated the underlying mechanisms at work in clearing RBC cells and recycling the iron they contained. The blood samples included blood from patients who underwent bypass surgeries.

Experiments using mice models have revealed that damaged RBCs in the bloodstream caused a quick increase in a monocyte population that gathered the damaged cells and took them both to the spleen and the liver. However, after several hours, the damaged RBCs were mostly found within macrophages that thrived only in the liver. And when the damaged RBCs were disposed of, the macrophages also disappeared.

"The mechanism we identified could be either helpful or damaging, depending on the conditions," said Filip Swirski, Ph.D., the study's senior author.

He explained that, if overactive, the mechanism will dispose of a large number of RBCs too fast. And if it was too slow or impaired in some other way, the reverse will occur, with too little RBCs removed, causing iron toxicity.

According to the researchers, further study is needed to explore how exactly the mechanism of RBC disposal happens to begin with, which will help in understanding how to control it in the presence of various health conditions.

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