New insights into platelet and leukocyte biology

The formed elements of blood perform essential functions and are necessary for survival. Red blood cells transport oxygen to tissues, platelets maintain hemostasis and leukocytes provide host defense. In addition to these autonomous roles, blood cells are able to communicate with one another to execute complex physiological processes. Platelet interactions with leukocytes and endothelium regulate diverse inflammatory responses. Platelet-monocyte interactions result in robust cytokine production in monocytes. Neutrophils receive signals from platelets which can result in transendothelial migration or neutrophil extracellular trap (NET) formation. Many of the mechanisms by which these processes are regulated have only been recently discovered. Here we report that platelets are able to sequester exogenous ribonucleic acid (eRNA). This uptake is time and dose dependent and is unique to platelets of the cells examined so far. Uptake of eRNA does not require activation of platelets or alter the ability of platelets to respond to thrombin. While the fate of this sequestered eRNA has yet to be determined, our observations represent the first report of this novel capacity of platelets. Our interest in platelet and leukocyte biology also led us to develop a genetic screen to identify genes required for NET formation. The nearly haploid human cell line, KBM-7, was determined to be competent to form NETs, and a retroviral gene-trap mutagenesis strategy was employed to generate a pool of mutants to assay for defects in NET formation. Due to technical limitations, the screen was unable to be executed as designed, but advances in bioinformatics may allow a modified version of the screen to be performed in the near future. Throughout the body of this work, we have used traditional techniques combined with modern innovations to interrogate the functions of platelets and leukocytes. The knowledge gained in these investigations will improve our understanding of these essential cells and provide new avenues for research and therapeutic interventions in the future.