Response “Re: Microparticles: markers and mediators of sepsis-induced microvascular dysfunction, immunosuppression, and acute kidney injury ”

We attempted to highlight progress in microparticle research and bring some clarity to a rapidly changing field that is still defining three major categories of extracellular vesicles: exosomes (smaller), microvesicles, and microparticles (larger). We thank Burger et al1 for pointing out the difficulties in describing what is present and what is active in a given system. The majority of microvesicles described by Cantaluppi et al2 were 60-160 nm, outside of our microparticle size range, 200-2000 nm. The key point by Burger et al1 is that Cantaluppi et al2 used a mixture of extracellular vesicles. These extracellular vesicle subtypes are typically distinguished by size, centrifugation method, and/or composition (including cell surface markers, lipids, and miRNA). The distinction between microvesicles and microparticles is subtle; they differ in size, but they are formed from the same blebbing of the plasma membrane, as confirmed microscopically by Cantaluppi et al.2 The size of the protrusions and accompanying vesicles corroborate their Nanosight sizing data; however, their flow cytometry data are consistent with larger microparticles (>200 nm). Both microvesicles and microparticles were likely present in their preparation. Such ambiguities can be clarified by using complementary methods, such as sizing larger particles by flow cytometry3 or characterizing smaller particles using fluorescent Nanosight detection. Unfortunately, their data cannot pinpoint whether the biological effect came from exosomes, microvesicles, or a small number of microparticles. miR126 can come from apoptotic bodies3, exosomes4, or microvesicles,2 making the context of other extracellular vesicle contents important for functional impact. Emerging techniques will enable these distinctions to be made more routinely.