PracticeUpdate Conference Series: ERS 2018

with proteins or bioactive lipid mediators and their precursors. Nanoparticle-based formulations have been used to deliver peptide fragments of AnxA1 to resolve inflammation in murine models of atherosclerosis. Mesenchymal stem cells may be viable delivery vehicles for microvesicles because they naturally release exosomes that suppress hypoxia in mice. Microvesicles are also amenable to targeting via incorporation of organ-specific homing peptides. Moreover, because the sequence directing mRNAs to the pathway of microvesicle secretion has been elucidated, microvesicles could be enriched for specific RNA species, enhancing their ability to deliver desired or therapeutic mRNA to target cells. Dr. Garner concluded that, for the first time, com- prehensive evaluation of microvesicles within bronchoalveolar lavage fluid and plasma of patients with chronic obstructive pulmonary disease demonstrated that numbers of neutrophil-derived microvesicles in this fluid correlate with indexes of functional and clinically relevant disease severity. The data strongly suggest that microvesicles in neutrophils of bronchoalveolar lavage fluid are a novel, clinically relevant biomarker of the severity of chronic obstructive pulmonary disease. Numbers of microvesicles may play a pathogenic role in the progression of COPD and be a potential target to modulate inflammation in the disease.

Soni et al used a set of conservative yet robust criteria to define microvesicles, namely, size, par- ent cell surface markers, and detergent sensitivity. Microvesicle numbers within bronchoalveolar lav- age fluid may be higher than they reported if some microvesicles do not express parent cell surface markers or express them at low levels. Though the results strongly suggested active communication between microvesicles and target cells, many unanswered questions remain about the precise nature of this interaction. Among these is whether this occurs on the surface of target cells or after microvesicle internalization. Microvesicles (0.05 to 1 μm) are composed of both exosomes and microparticles. Microvesicles are emerging as novel determinants of paracellular communication. Released by most eukaryotic cells, microvesicles can transfer proteins, lipids, nucleic acids, and cytosolic material. Microvesicles origi- nating from different cells differ in composition and biological function. The biological impact of neutrophil microvesi- cles is intriguing because these microstructures express >300 proteins that vary in relation to the stimulus and microenvironment that leads to their production. It is therefore plausible that neutrophil microvesicle subtypes can elicit distinct down- stream effects. Using microvesicles as novel therapeutic tools in inflammatory diseases is a promising clinical approach because microvesicles can be enriched

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ERS 2018 • PRACTICEUPDATE CONFERENCE SERIES 15