Arthritis, platelets, and inflammation

As I mentioned in my last post, this has been a watershed week in two areas I'm greatly interested in. Two major discoveries were published last week that are in areas of great interest for myself. My first post concentrated on one of my favourite parts of the cell - mitochondria. The second article I want to blog about is a blast from my past, and involves inflammation - the major way our immune system gets rid of bacteria, and ironically, the cause of many human diseases.

This paper discusses the role platelets - the miniature cells that help our blood clot - play in making some forms of arthritis worse. It also addresses the role of a biological mystery - microparticles - play in mediating disease.



Platelets main role is to form blood clots - upon breaking a blood vessel they encounter the proteins that "glue" our cells together. Upon identifying these proteins (and protein products formed when this "glue" is exposed to blood) platelets glom together, forming a clot. At the same time they release chemical signals that inform our bodies that the blood vessel is damaged and that an immune response is needed. In many cases those chemical signals are the first warnings our immune system has that something is wrong. But in a few cases damage caused by the immune system results in platelet activation, in which case those chemicals tend to aggravate the underlying condition.

The second half of this story surrounds microparticles (image at left) - microscopic sized fragments of cells that are found in the various fluid of our bodies. Even today the source, cause and purpose of these particles remains elusive. Whether they're deliberate products that have an evolutionarily-derived purpose, or whether they're an abnormality caused by biological malfunction, is not known. A large range of cells are known to produce these particles, but in only a small number of cases do we know how, and why, these are made.

The authors of this paper have tested a couple of fairly simply hypotheses - do plateltes form microparticles during an inflammatory disease (arthritis), and do those microparticles alter the disease itself?

The answer to the former question is a resounding 'yes'; the number of platelet-derived microparticles increases by a huge amount during arthritis. Not only that, but the researchers were able to determine that one single receptor - the collagen receptor GPVI. Collagen, by the way, is one of the glues which hold our cells together. By blocking the interaction of GPVI with collagen this group was able to both stop microparticle generation, and reduce the severity of arthritis. The image to the left shows a platelet releasing microparticles.

Which leads us to the second question they asked - do these microparitcles affect the disease? Obviously the answer is 'yes', as removing the particles reduced the severity of the disease. Exactly how this occurs is a bit of a mystery - although we know a chemical signal called "interleukin-1" is involved.

What this means for patients is twofold - first of all, it validates the idea that the presence of these microparticles may be a way to detect disease. Emphasis on the "may" - we simply do not know enough about these particles to really make any firm predictions at this point. The second thing this does for patients is open the door to new therapies, targeting either GPVI or the microparticles themselves.

Boilard E, Nigrovic PA, Larabee K, Watts GF, Coblyn JS, Weinblatt ME, Massarotti EM, Remold-O'Donnell E, Farndale RW, Ware J, & Lee DM (2010). Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science (New York, N.Y.), 327 (5965), 580-3 PMID: 20110505