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Please squeeze the red blood cells types in here and actually watch the A traveling bag of hemoglobin. That’s very tiny tweezers, squeezing the RBCs how most people think of the poor, unthrough a restricted diameter is the best cells talking to each other via some sort of molecular signaling,” says Spence. appreciated red blood cell (RBC), acway to do this. That signaling is the aforementioned cording to Dana Spence of Wayne State RBCs are ~7–8 µm in diameter, and University. Certainly, supplying oxygen the body’s smallest vessels—the capillar- ATP release. With a luciferin/luciferase assay, Spence and colleagues detect ATP to living tissue is an important task, but ies and the arterioles—are ~10–100 µm production from RBCs in the with no nucleus and no mitopresence or absence of two chondria, the RBC at first drugs, pentoxifylline and iloglance appears to be a very prost, that improve blood flow boring cell. But in the July 15 in vivo. Pentoxifylline is issue of Analytical Chemistry (pp 5133–5138), Spence and thought to make the RBC his colleagues attempt to polmore deformable, which in ish up this cell’s dull image by theory should cause the cell to using a continuous-flow analyrelease more ATP. Indeed, with sis system to show how RBCs the microflow system, the reare involved in an intricate insearchers measured an increase tercellular conversation with in ATP concentration in the platelets—a conversation that presence of the drug. Iloprost has the potential to affect carhas been reported to stimulate diovascular health. ATP release from RBCs, and Spence’s interest in the the researchers quantitatively RBC began as a collaboration measured this release as well. with Randy Sprague, a physiIn addition, Spence and colcian at St. Louis University. leagues showed that they could Sprague had noticed that if detect the result of that ATP Spence’s microflow system is helping to bring the humble RBC he pushed buffer containing signal, the release of NO by the recognition it deserves. RBCs through vessels in a platelets. The researchers treatlung, the vessels would dilate, ed the RBCs with pentoxifylin diameter, so at first glance, it seems line or iloprost and then flowed them but in the absence of RBCs, this effect that the RBCs should flow through through the microbore tubing with disappeared. Sprague deduced that the these vessels without deforming. Spence platelets and an NO-detection agent, diRBCs were actually releasing adenosine uses door crowding as an analogy to aminofluorofluorescein; both drugs intriphosphate (ATP), which stimulated what is happening in the vessels. “You creased NO production by platelets. the endothelial cells to release NO, a and I could both go through that door In the future, the researchers would well-known vasodilator that has been easily, but if we had to go through at like to make their model system more studied by the scientific community for the same time, we might squeeze each authentic by adding more cell types to years. Eventually, “he wanted to more the mix. “We have the red cells and the quantitatively measure the ATP that was other,” he explains. He adds that the more “scientific” explanation is that platelets,” Spence says. “Let’s go ahead being released from the RBCs,” says blood is a non-Newtonian fluid, which and actually add the endothelium to it.” Spence. “So a few years back, I started collaborating with Randy to make these means that the RBCs all crowd together This improved model could eventually at the center of the tube (where the rebe used to study the cardiovascular eftypes of measurements in our microsistance is minimal) and further squeeze fects of diseases such as cystic fibrosis, flow systems.” and deform each other. diabetes, and sickle-cell anemia. Spence’s microflow systems turned Spence and colleagues’ previous “You caught me right at a neat periout to be a very good mimic of living work has focused on the behavior of inod in our group because we have startvessels. Previous studies on RBCs had dividual types of cells in these microflow ed actually moving more toward the been carried out in a static system that ignored an important aspect of the cells’ tubes or in microfluidic devices; the cur- medical side of things,” Spence says. rent work is the first time they’ve stud“Some of the things we are learning— behavior: to stimulate the RBCs to reit’s truly amazing!” a lease ATP, they have to be physically de- ied the behavior of two cell types at the —Jennifer Griffiths formed. Short of pinching the cells with same time. “We can put multiple cell A U G U S T 1 , 2 0 0 7 / A N A LY T I C A L C H E M I S T R Y
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