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Exosome composition Exosome composition varies depending on the cell type of origin.

Nevertheless, exo- somes contain a number of common protein components (Thery et al., 2001). Several adhesion molecules such as intercellular adhesion molecule-1, CD146, CD9, milk-fat-globule EGF-factor VIII (MFG-E8), CD18, CD11a, CD11b, CD11c, CD166 and LFA- 3/CD58 have also been identified in exosomal preparations ( Thery et al., 2001; Mears et al., 2004 ). In addition, several proteins involved in apoptosis are present on exosomes including thioredoxin peroxidase II, Alix, 14-3-3 and galectin 3. Exosomes also contain heat- shock proteins Hsp70 and Hsp90, which can facilitate peptide loading onto major histocompatibility complex (MHC)I and MHCII (Gastpar et al., 2005). One of the characteristic features of exosomes is the tetraspanins, which include CD9, CD63, CD81 and CD82. Exosomes also carry some cell-specific proteins like MHCII and CD86 present only on exosomes isolated from antigen-presenting cells (APCs) (Segura et al., 2005) and MFG-E8/lactadherin present on exosomes from immature DCs (Veron et al., 2005). Exosomes are also enriched in proteins that participate in vesicle formation and trafficking like the lyso- bisphosphatidic acid (LBPA)-binding protein Alix (Futter et al., 2007). Other proteins detected on exosomes are the metabolic enzymes such as peroxidases, pyruvate and lipid kinases and eno- lase-1 (Hegmans et al., 2004). Consistent with their endosomal origin, exo- somes typically do not contain endoplasmic reticulum, mitochondria or nuclear proteins. Similar to proteins, lipids present on exosomes are char- acteristic of the cell origin, with most of the lipid analytical work being performed on exosomes derived from reti- culocytes (Vidal et al., 1989), mast cells (Laulagnier et al., 2004), B lymphocyte cell lines (Wubbolts et al., 2003) and human DCs (Laulagnier et al., 2004). The typical lipid composition of mast cell-derived exosomes includes lysophosphatidylcholine, sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, cholesterol and diglyceride (Laulagnier et al., 2004).
Futter CE, White IJ. Annexins and endocytosis. Traffic 2007;8: 951958. Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res 2005;65:52385247. Hegmans JP,BardMP, HemmesA,LuiderTM, Kleijmeer MJ,PrinsJB, Zitvogel L, Burgers SA, Hoogsteden HC, Lambrecht BN. Proteomic analysis of exosomes secreted by human mesothelioma cells. Am J Pathol 2004;164:18071815. Laulagnier K, Motta C, Hamdi S, Roy S, Fauvelle F, Pageaux JF, Kobayashi T, Salles JP, Perret B, Bonnerot C, Record M. Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem J 2004;380:161171. Mears R, Craven RA, Hanrahan S, Totty N, Upton C, Young SL, Patel P, Selby PJ, Banks RE. Proteomic analysis of melanoma-derived exo- somes by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Proteomics 2004;4:40194031. Segura E, Amigorena S, Thery C. Mature dendritic cells secrete exosomes with strong ability to induce antigen-specific effector immune responses. Blood Cells Mol Dis 2005;35:8993. Veron P, Segura E, Sugano G, Amigorena S, Thery C. Accumulation of MFG-E8/lactadherinon exosomesfrom immaturedendritic cells. Blood Cells Mol Dis 2005;35:8188. Vidal M, Sainte-Marie J, Philippot JR, Bienvenue A. Asymmetric distribution of phospholipids in the membrane of vesicles released during in vitro maturation of guinea pig reticulocytes: evidence pre- cluding a rolefor aminophospholipid translocase.JCell Physiol 1989; 140:455462. Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Mobius W, Hoernschemeyer J, Slot JW, Geuze HJ, Stoorvogel W. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential mplications for their function and multivesicular body formation. J Biol Chem 2003;278:1096310972. Thery C, Boussac M, Veron P, Ricciardi-Castagnoli P, Raposo G, Garin J, Amigorena S. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol 2001;166:73097318.

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