Red blood cells are the most abundant anucleate cell type in the human body, Yet little is known about them apart from their vital role in transporting oxygen to organs and tissues. Almost all of us know that blood vessels signal bone marrow for red blood cell production in case of low volume of blood or decreased number of red blood cells. But a research team, led by a scientist at Weill Cornell Medical College, has discovered that red blood cells perform a second vital function: angiogenesis, the creation of new blood vessels from those that already exist.

These investigators showed that red blood cells supply a lipid that is known to regulate angiogenesis, sphingosine-1-phosphate (S1P). Angiogenesis is necessary for growth, repair and regenerative processes that require increased blood flow and oxygenation of tissues.

Given its role in creating new blood vessels, scientists recognize S1P as vital to human health — and a player in some diseases, such as cancer. And although S1P is known to be blood borne, no one realized until this study that S1P is supplied by red blood cells to control blood vessel growth, researchers claimed.

The association between red blood cells and blood vessel formation was missed for so long, but underlying researchers unfolded the link by delving into what role this lipid plays in diseases in which red blood cells are defective.

This study demonstrated that production of S1P by red blood cells is crucial in the formation and development of an embryo. Embryonic development of mutant mice with red blood cells that lacked S1P stopped mid-gestation, but mutant embryos in which S1P was restored developed normally. An embryo cannot develop, if angiogenesis is impaired.

Knowing  that red blood cells are responsible for supplying S1P, the next question is whether S1P plays a role in abnormal blood vessels in various tissues when red blood cells are diseased, such as in sickle cell disease, thalassemia, infectious diseases, and cerebral malaria.

In these conditions, blood vessels become diseased and make organs fail. And if S1P is indeed involved in these disorders, which are unknown yet, drugs that block this lipid could be helpful. Diseased blood cells that burst or leak, for example, can spill too much S1P into tissue, resulting in unhealthy blood vessels and angiogenesis.

Such inhibitor is already on the market. As S1P is also known to modulate immune system function, an S1P inhibitor has been approved to treat the inflammatory disease multiple sclerosis. Other S1P inhibitors are also being tested to block immune function or excessive angiogenesis, such as occurs in cancer and other disorders such as psoriasis and rheumatoid arthritis.

But erythrocytes not only create new blood vessels, they also have another new role that was recently revealed by researchers. Having their biconcave shape they also take part in hemostasis and thrombosis. It was previously recognized that increased aggregation of red cells and changes in blood viscosity (which is largely determined by red cells) contribute to the risk of thrombosis. However, the red cell does not appear to be a mere bystander in blood clot formation because other studies have shown that red blood cells influence fibrin network structure and pore size. Recent studies have shown that red cells also influence the viscoelastic properties of the clot and slow down fibrinolysis by different mechanisms not only based on reduced penetration of the clot by the fibrinolytic enzymes.

They do this because red cells in the clot produce a polyhedral shape, which as it turns out, leads to an almost perfect seal of the clot, due to maximum cell-cell interaction and minimum interstitial space. 

White blood cells also was reported to play role not only in immune system, but also in hemostasis and thrombosis. Red blood cells also modulates immune response.

Platelets have additional role other than in coagulation, as it is revealed that they might induce inflammatory response likewise macrophages and take part in the immune system.

All these new insights suggest that there is no cross border in the role of blood components and their role may overlap.

Based on these findings, the notion that the red cell would be an innocent bystander when it comes to hemostasis and thrombosis can no longer be supported. It is perhaps not coincidental that the most abundant anucleate blood cell (the red cell) plays an important role together with the second most abundant and only other anucleate blood cell (the platelet) in the stemming of bleeding.

These fundamental discoveries about the role of the red cell in clot formation may lead to future new developments in the treatment of diseases associated with bleeding or thrombosis.

COPYRIGHT: This article is property of We Speak Science, a nonprofit institution co-founded by Dr. DetinaZalli (Harvard University) and Dr. ArgitaZalli (Imperial College London).