Chemical Conversation: Red blood cells send a signal that makes platelets less sticky

Primarily known for their work hauling oxygen to tissues throughout the body, red blood cells may also play a part in regulating activities of another blood component. The cells can release a chemical that signals blood-clotting platelets to become less sticky and therefore less likely to clog a narrow vessel, chemists report.

Red blood cells change shape as they maneuver through the curves and narrows of the body’s circulatory system. As they flex, the cells release small amounts of adenosine triphosphate (ATP), an energy-storing molecule, into the bloodstream. Earlier research had established that ATP can stimulate cells lining the walls of blood vessels to produce nitric oxide (NO), which causes the walls to relax, allowing blood to flow more easily.

Researchers also knew that platelets respond to ATP in the bloodstream by producing NO, which reduces their tendency to clump. Using a technique that mimics the natural flow of blood cells, Dana Spence and his colleagues at Wayne State University in Detroit have now shown that platelets respond specifically to ATP released by red blood cells in a way that promotes blood flow.

“It’s possible that red cells and platelets are communicating and working together,” comments Randy Sprague of Saint Louis University in Missouri.

Spence and his collaborators pumped red blood cells and platelets through tubing 50 micrometers in diameter. They used a standard method to track ATP release within the tube, adding chemicals that react with ATP to produce a fluorescent signal. To track NO, they used a different fluorescent molecule that they trapped within the platelets. “We made all these measurements in the blood,” Spence says. “We had platelets in there, red blood cells in there; they were flowing.”

To establish the connection between ATP from red blood cells and NO production in platelets, the researchers conducted a variety of tests in which they modified either ATP production by red blood cells or the platelets’ response to ATP. Two drugs, iloprost and pentoxyfilline, increased ATP production by red blood cells and NO production by platelets, the researchers report in the July 15 Analytical Chemistry. Researchers had known that these drugs increase blood flow, but the new study establishes a mechanism for how they do so, Spence says.

The results may help researchers understand circulatory problems in diabetes patients. Studies have shown that red blood cells in people with diabetes have limited flexibility and a reduced capacity to release ATP.

Spence and other researchers have gathered “strong evidence that there’s something wrong with this pathway in diabetic patients,” says pathologist Rakesh Patel of the University of Alabama at Birmingham. If red blood cells play a role in controlling both platelets and blood vessels, they represent a new target for drugs that could fight diabetes symptoms, he adds.

“Even 2 or 3 years ago, no one in diabetes or in red cell biology would have thought there was a connection,” Patel says. “These studies open up a new avenue of thinking.”