Platelet message and microarrays

Platelets are anucleate, and until the late 1980s it was thought that circulating platelets have little residual RNA message. But in 1988 Newman et al (J Clin Invest. 1988;82:739-743) showed that one can use RT-PCR to amplify platelet-specific messages from purified peripheral blood platelets. Since then, numerous laboratories have taken advantage of this observation to clone and identify mutations and determine relative levels of platelet-specific messages. In time, it has been assumed that platelets are actually a rich source of platelet message. With the more recent development of microarrays and related approaches for widespread transcript analysis, one can envision an even greater use of circulating platelet RNA. One might expect to more fully define the genes representative of late megakaryocyte development. Perhaps these approaches would define gene products whose expression levels correlate with an increased risk of thrombotic or other clinical states.

The manuscript by Gnatenko and colleagues (page 2285) represents an early use of such a strategy, and not only provides exciting new information but also grounds expectation in reality. Platelets are not a rich source of message. First, the vast majority of messages actually are derived from the mitochondria. Second, even with taking extra steps to ensure purity, the top 3 messages determined by microarray were white cell or red cell messages. On the plus side, the study clearly defined the relative abundance of a number of platelet-specific genes, including the demonstration that chemokines such as PF4, PBP, and RANTES are among the most abundant messages, pointing to the importance of platelets in both thrombosis and inflammation. Also, 2 previously unrecognized messages for neurogranin, a protein kinase C substrate, and clusterin, a complement lysis inhibitor, are present in platelets. It is hoped that with further technical improvements, additional insights and clinical usage can come from analysis of this ready source of megakaryocyte/platelet message.