"The Role of Microparticles in the Pathogenesis of Inflammation & Autoimmune Disease"

David Pisetsky, M.D., Ph.D.
Professor of Medicine and Immunology
Duke University Medical Center

Microparticles (MPs) are small membrane-bound vesicles that emanate from dead and dying cells to serve as signaling elements with potent pro-inflammatory and pro-thrombotic activity.  MPs range in size from approximately 0.1 to 1.0 microns and are part of the spectrum of extracellular vesicles (EVs) present in the blood and other biological fluids.  MPs are routinely assayed by flow cytometry, with cell surface markers allowing identification of their origin.  In addition to their content of membrane and cytoplasmic molecules, MPs are an important source of extracellular nucleic acids, both DNA and RNA.  As such, MPs have the ability to transfer genetic information from one cell to another.  Levels of MPs are elevated in many diseases characterized by inflammation or vasculopathy, suggesting that MPS can drive key events in pathogenesis via their content of bioactive molecules.  In systemic lupus erythematosus (SLE), a prototypic autoimmune disease characterized by the production of antinuclear antibodies, MPs can serve as a source of DNA antigen for the formation of immune complexes; in this setting, MPs are decorated by IgG autoantibodies as well as complement. Future studies are addressing the biomarker function of MPs and developing strategies that can reduce particle production to attenuate disease manifestations.