Most high schoolers - indeed, some elementary schoolers - are aware that platelets play a role in blood clotting. As is the scientific community: "98 percent of the work that has been done on platelets has been done on their role in thrombus formation" or blood clotting, David Lee told BioWorld Today.
But the times they are a-changing. In the Jan 29, 2010, issue of Science, Lee and his colleagues published studies showing that platelets play a role in inflammatory arthritis, adding to a growing realization that "platelet functionality extends significantly beyond thrombus formation."
Lee, who is at Brigham and Women's Hospital, and colleagues from Harvard Medical School, Children's Hospital Boston, the University of Cambridge and the University of Arkansas began searching for a role for platelets in arthritis because within the scientific community there has been "a growing realization" that platelets contribute to inflammatory processes, Lee said.
Previous studies had shown that platelets can be found in arthritic joints. But the idea that platelets contribute to pathology in autoimmune disease is a new one.
Part of the reason that Lee and his team were able to identify the importance of platelets in rheumatoid arthritis is that they realized early on in screening experiments that whole platelets do not appear to be what causes problems in rheumatoid arthritis. Instead, smaller particles - descriptively called microparticles - bud off when the platelets are activated. And standard platelet detection methods are usually set up to ignore small particles, which are assumed to be mere artifacts.
"We had to change the way these things are analyzed," Lee explained. "And when [first author Eric Boilard] did that: Boom! There were tons of them" - the authors found that synovial fluid, which cushions the joints, contained orders of magnitude more platelet-derived microparticles than blood does. At least if that synovial fluid came from patients with rheumatoid arthritis.
Patients with osteoarthritis - a form of arthritis that has different inflammatory mechanisms - had no microparticles in their synovial fluid.
The authors next tested the role of platelets in the development of arthritis in vivo. They used so-called serum transfer experiments, where arthritis is induced in animals by transferring serum from arthritic ones. If Lee and his team removed platelets from the serum before transferring it, the animals developed a milder form of arthritis.
Lee and his team went on to study the details of how platelets are activated in arthritis, and found that the activation pathway is different from the mechanisms that activate pathways for clotting. Instead, Lee said, cell culture experiments modeling the environment within the synovial joint showed that collagen in the extracellular matrix that is secreted by cells in the synovial joint activates platelets via a specific collagen receptor, the glycoprotein VI receptor, inducing the shedding of microparticles. The microparticles in turn contain platelet-derived cytokines, which they unload in the joints, promoting inflammation.
Lee stressed that his team has no direct therapeutic data yet and any practical use of the findings is a long way off. Nevertheless, the independence of the activation pathway from clotting pathways, as well as the fact that humans lacking the receptor have only "mild bleeding tendencies" both potentially bode well for therapeutic harnessing of the findings. And, Lee added, any possible treatments that target platelets would have another thing going for them: They would not be immunosuppressive.