Proteomic Analysis of Dendritic Cell-Derived Exosomes: A Secreted Subcellular Compartment Distinct from Apoptotic Vesicles

摘要

Dendritic cells constitutively secrete a population of small (50-90 nm diameter) Ag-presenting vesicles called exosomes.When sensitized with tumore antigenic peptides, densritic cells produce exosomes,which stimulate anti-tumor immune responses and the rejection of established tumors in mice. Using a systematic proteomic approach, we establish the first extensive protein map of a particular exosome population; 21 new exosomal proteins wre thus identified. Most proteins present inexosomes are related to endocytic compartments. New exosomal residents include cytosolic proteins most likely involved inexosome biogenesis and function, mainly cytoskeleton-related (confilin, profilin I, and elongation factor 1#alpha#) and ntracellular membrane transport and signaling factors (such as several annexins, rab 7 and 11, rap1B, and synthenin). Importantly, we also identified a novel category of exosomal proteins related to appoptosis: thioredoxin peroxidase II,Alix, 14-3-3, and galectin-3. Thse findings led us to analyze possible structural relationships between exosomes and microvesicles released by apoptotic cells. We show that although they both represent secreted populations of membrane vesicles relevant to immune responses, exosomes and apoptotic vesicles are biochemically and morphologically distinct. Therefore, in addition to cytokines, dendritic cells produce a specific population of membrane vesicles, exosomes, with unique moeluclar composition and strong immunostimulating properties.