exosomes composition

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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 on to 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 e xosomes isolated from antigen-presenting cells (APCs) ( Segura et al., 2005) and MFG-E8/lactadherin present on exosomes from immature DCs (V eron 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- s omes typically do not contain endoplasmic reticulum, mitochondria or nuclear proteins. Similar to proteins, lipids present on e xosomes are char- acteristic of the cell origin, with m ost 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 c ell-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: 951  958. Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G. Heat s hock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Ca ncer Res 2005;65:5238  5247. 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;164:1807  1815. 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;380:161  171. 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;4:4019  4031. Segura E, Amigorena S, Thery C. Mature dendritic cells secrete exosomes with strong abilit y to induce antigen-specific effector immune responses. Blood Cells Mol Dis 2005;35:89  93. Veron P, Segura E, Sugano G, Amigorena S, Thery C. Accumulation of MFG-E8/lactadherinon exosomesfrom immaturedendritic cells. Blood Cells Mol Dis 2005;35:81  88. 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; 140:455  462.  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 f or their function and multivesicular body formation. J Biol Chem 2003;278:10963  10972.  Thery C, Boussac M, Veron P, Ricciardi-Castagnoli P, Raposo G, Garin J, Ami gorena S. Proteomic analysis of dendritic cell- derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol 2001;166:7309  7318.

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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: 951 –958.

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;65:5238 –5247.

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;164:1807 –1815.

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;380:161 –171.

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;4:4019 –4031.

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;35:89 –93.

Veron P, Segura E, Sugano G, Amigorena S, Thery C. Accumulation of MFG-E8/lactadherinon exosomesfrom immaturedendritic cells.

Blood Cells Mol Dis 2005;35:81 –88.

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;

140:455 –462.

  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;278:10963 –10972.  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;166:7309 –7318.