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*
Institut National de la Santé et de la Recherche Médical, Unité 520, Institut Curie, Paris, France;
Commissariat à l’Energie Atomique, Laboratoire de Chimie des Protéines, Grenoble, France;
Department of Biotechnology and Biological Sciences, Second University of Milan, Milan, Italy; and
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 144, Institut Curie, Paris, France
Dendritic cells constitutively secrete a population of small
(50–90 nm diameter) Ag-presenting vesicles called exosomes. When
sensitized with tumor antigenic peptides, dendritic 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 were thus identified. Most
proteins present in exosomes are related to endocytic compartments. New
exosomal residents include cytosolic proteins most likely involved in
exosome biogenesis and function, mainly cytoskeleton-related (cofilin,
profilin I, and elongation factor 1
) and intracellular membrane
transport and signaling factors (such as several annexins, rab 7 and
11, rap1B, and syntenin). Importantly, we also identified a novel
category of exosomal proteins related to apoptosis: thioredoxin
peroxidase II, Alix, 14-3-3, and galectin-3. These 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 molecular composition and strong
immunostimulating properties.
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A. E. Morelli, A. T. Larregina, W. J. Shufesky, M. L. G. Sullivan, D. B. Stolz, G. D. Papworth, A. F. Zahorchak, A. J. Logar, Z. Wang, S. C. Watkins, et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells Blood, November 15, 2004; 104(10): 3257 - 3266. [Abstract] [Full Text] [PDF]
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