Further comments on platelet proteomics in Transfusion Medicine.

Abstract

Dear Sir, We read with interest the comments submitted by Drs. Lello Zolla and Angelo D’Alessandro, entitled: “Response to “Platelets proteomics in Transfusion Medicine: a reality with a challenging but promising future””. In this letter, the Authors replied to our reaction to the impact of platelets proteomics in Transfusion Medicine1. The major trigger that makes us to give further comments on the letter by Drs. Zolla and D’Alessandro is to discuss the correct application of integrated “-omics” in the collection of knowledge about the platelets and, in turn, studies on the prolongation of platelet storage. We agree with the statement regarding the link between integrated “-omics” and platelet storage raised by Drs. Zolla and D’Alessandro, because we never ignored the power of such integration: indeed, we performed and promoted not only such a combination but also a mixture of classical technologies with the novel “omics”, considering this an advantage that should not be ignored in basic scientific studies2. However, for a successful proteomics (or “omics”) analysis of platelets and clear knowledge of the platelet proteome, well-defined and high purity platelets are essential3,4. In this regard, the common concept in the world of proteomics is: “if a defined sample is put into a mass spectrometer (MS), a defined list of proteins comes out of the MS but if an undefined sample is put into a MS, an undefined protein coverage comes out of the MS”. It is reasonable to consider platelets stored for 9 to 15 days at 22 °C as an undefined sample. The other point that we must stress is that a “supervised” application of combined “omics” is essential when studying the prolongation of platelet storage. Between 2005 and 2012, Badlou et al. showed how metabolic suppression of isolated platelets can serve for better solutions to preserve platelet function and viability during prolonged storage5. A good example of a “supervised” application of “integrated -omics” is to study the storage of platelets in such a state. We are very happy that Drs. Zolla and D’Alessandro discussed post-translational modifications such as phosphorylation in platelet storage lesions. However, based on classical theory, protein synthesis starts in the nucleus. Indeed, we argue that platelets have no nucleus and it is, therefore, reasonable to consider that protein synthesis is inactive and, in turn, that post-translational modifications may also be inactive. Thus, if post-translational modifications of proteins observed in platelets are not processed by the classical pathway such modifications must be mediated by other pathways, which remain to be elucidated. Based on the fact that platelets have no nucleus, we argue that miRNA studies are the first choice technique for studying platelets, while proteomics should be a complementary, albeit very important, technique rather than the first choice. In conclusion, there are three essential points to take into consideration in the collection of knowledge about platelets with the purpose of improving platelet storage time: (i) the use of well-defined, purified platelet concentrate fractions; (ii) the use of fresh platelet concentrates instead of old ones stored for 2 weeks at room temperature; and (iii) the correct application of integrated “-omics” in a “responsive design” with respect to the platelet proteome and platelet storage studies.