Exosomal lipid composition and the role of ether lipids and phosphoinositides in exosome biology
2018; Elsevier BV; Volume: 60; Issue: 1 Linguagem: Inglês
10.1194/jlr.r084343
ISSN1539-7262
AutoresTore Skotland, Nina P. Hessvik, Kirsten Sandvig, Alicia Llorente,
Tópico(s)Viral Infections and Vectors
ResumoExosomes are a type of extracellular vesicle released from cells after fusion of multivesicular bodies with the plasma membrane. These vesicles are often enriched in cholesterol, SM, glycosphingolipids, and phosphatidylserine. Lipids not only have a structural role in exosomal membranes but also are essential players in exosome formation and release to the extracellular environment. Our knowledge about the importance of lipids in exosome biology is increasing due to recent technological developments in lipidomics and a stronger focus on the biological functions of these molecules. Here, we review the available information about the lipid composition of exosomes. Special attention is given to ether lipids, a relatively unexplored type of lipids involved in membrane trafficking and abundant in some exosomes. Moreover, we discuss how the lipid composition of exosome preparations may provide useful information about their purity. Finally, we discuss the role of phosphoinositides, membrane phospholipids that help to regulate membrane dynamics, in exosome release and how this process may be linked to secretory autophagy. Knowledge about exosome lipid composition is important to understand the biology of these vesicles and to investigate possible medical applications. Exosomes are a type of extracellular vesicle released from cells after fusion of multivesicular bodies with the plasma membrane. These vesicles are often enriched in cholesterol, SM, glycosphingolipids, and phosphatidylserine. Lipids not only have a structural role in exosomal membranes but also are essential players in exosome formation and release to the extracellular environment. Our knowledge about the importance of lipids in exosome biology is increasing due to recent technological developments in lipidomics and a stronger focus on the biological functions of these molecules. Here, we review the available information about the lipid composition of exosomes. Special attention is given to ether lipids, a relatively unexplored type of lipids involved in membrane trafficking and abundant in some exosomes. Moreover, we discuss how the lipid composition of exosome preparations may provide useful information about their purity. Finally, we discuss the role of phosphoinositides, membrane phospholipids that help to regulate membrane dynamics, in exosome release and how this process may be linked to secretory autophagy. Knowledge about exosome lipid composition is important to understand the biology of these vesicles and to investigate possible medical applications. Exosomes and microvesicles are considered to be the main types of extracellular vesicles (EVs) released by living cells (1Yáñez-Mó M. Siljander P.R. Andreu Z. Zavec A.B. Borràs F.E. Buzas E.I. Buzas K. Casal E. Cappello F. Carvalho J. et al.Biological properties of extracellular vesicles and their physiological functions.J. Extracell. Vesicles. 2015; 4: 27066Crossref PubMed Scopus (2910) Google Scholar, 2György B. Szabo T.G. Pasztoi M. Pal Z. Misjak P. Aradi B. Laszlo V. Pallinger E. Pap E. Kittel A. et al.Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles.Cell. Mol. Life Sci. 2011; 68: 2667-2688Crossref PubMed Scopus (1472) Google Scholar, 3Hessvik N.P. Llorente A. Current knowledge on exosome biogenesis and release.Cell. Mol. Life Sci. 2018; 75: 193-208Crossref PubMed Scopus (1247) Google Scholar, 4van Niel G. D'Angelo G. Raposo G. Shedding light on the cell biology of extracellular vesicles.Nat. Rev. Mol. Cell Biol. 2018; 19: 213-228Crossref PubMed Scopus (3351) Google Scholar, 5Colombo M. Raposo G. Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles.Annu. Rev. Cell Dev. Biol. 2014; 30: 255-289Crossref PubMed Scopus (3594) Google Scholar). Exosomes are smaller than 150 nm in diameter and are released from cells after fusion of multivesicular bodies (MVBs) with the plasma membrane; whereas, microvesicles bud from the plasma membrane and are typically 100–1,000 nm in diameter. Intracellular vesicular transport is a main cellular activity that has been thoroughly studied for many years (6Bonifacino J.S. Vesicular transport earns a Nobel.Trends Cell Biol. 2014; 24: 3-5Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar). In contrast, the vesicular transport of molecules from cell to cell via EVs is a process that has only recently started to be investigated (7Lo Cicero A. Stahl P.D. Raposo G. Extracellular vesicles shuffling intercellular messages: for good or for bad.Curr. Opin. Cell Biol. 2015; 35: 69-77Crossref PubMed Scopus (311) Google Scholar, 8Martins V.R. Dias M.S. Hainaut P. Tumor-cell-derived microvesicles as carriers of molecular information in cancer.Curr. Opin. Oncol. 2013; 25: 66-75Crossref PubMed Scopus (169) Google Scholar, 9Record M. Carayon K. Poirot M. Silvente-Poirot S. Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies.Biochim. Biophys. Acta. 2014; 1841: 108-120Crossref PubMed Scopus (589) Google Scholar, 10Tkach M. Thery C. Communication by extracellular vesicles: where we are and where we need to go.Cell. 2016; 164: 1226-1232Abstract Full Text Full Text PDF PubMed Scopus (2005) Google Scholar). This review will focus on exosomes and, in particular, on their lipids, a topic that has important implications for the biology of exosomes. Exosomes correspond to the intraluminal vesicles (ILVs) of MVBs (also called late endosomes), organelles of the endocytic pathway. These organelles typically have a diameter of 250–1,000 nm and contain numerous ILVs (often ˃30) with a diameter of 50–100 nm (11Huotari J. Helenius A. Endosome maturation.EMBO J. 2011; 30: 3481-3500Crossref PubMed Scopus (1529) Google Scholar, 12Record M. Subra C. Silvente-Poirot S. Poirot M. Exosomes as intercellular signalosomes and pharmacological effectors.Biochem. Pharmacol. 2011; 81: 1171-1182Crossref PubMed Scopus (416) Google Scholar). The fusion of MVBs with the plasma membrane results in exosome release (Fig. 1). MVBs can also fuse with lysosomes and with autophagosomes, the latter resulting in amphisomes (Fig. 1). It should be noted that these organelles can also fuse with the plasma membrane and release their content (13Ponpuak M. Mandell M.A. Kimura T. Chauhan S. Cleyrat C. Deretic V. Secretory autophagy.Curr. Opin. Cell Biol. 2015; 35: 106-116Crossref PubMed Scopus (299) Google Scholar, 14Claude-Taupin A. Jia J. Mudd M. Deretic V. Autophagy's secret life: secretion instead of degradation.Essays Biochem. 2017; 61: 637-647Crossref PubMed Scopus (32) Google Scholar, 15Andrews N.W. Regulated secretion of conventional lysosomes.Trends Cell Biol. 2000; 10: 316-321Abstract Full Text Full Text PDF PubMed Scopus (278) Google Scholar). It can be expected that the specific lipid composition of exosomes resembles that of ILVs. Not much is known about the lipid composition of ILVs, but they seem to contain more cholesterol (CHOL), sphingolipids, phosphatidylinositol (PI)-3-phosphate [PI(3)P], and bis(monoacylglycero)phosphate (BMP) (also called lysobisphosphatic acid) than the limiting membrane of MVBs (11Huotari J. Helenius A. Endosome maturation.EMBO J. 2011; 30: 3481-3500Crossref PubMed Scopus (1529) Google Scholar, 16Möbius W. van Donselaar E. Ohno-Iwashita Y. Shimada Y. Heijnen H.F. Slot J.W. Geuze H.J. Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway.Traffic. 2003; 4: 222-231Crossref PubMed Scopus (346) Google Scholar). Moreover, the lipid composition of ILVs seems to vary depending on the maturation stage of MVBs, with CHOL being especially enriched in ILVs at early stages and BMP at later stages (16Möbius W. van Donselaar E. Ohno-Iwashita Y. Shimada Y. Heijnen H.F. Slot J.W. Geuze H.J. Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway.Traffic. 2003; 4: 222-231Crossref PubMed Scopus (346) Google Scholar). The high content of CHOL and the low content of BMP in exosomes are in agreement with the idea that exosomes originate from MVBs at earlier stages (16Möbius W. van Donselaar E. Ohno-Iwashita Y. Shimada Y. Heijnen H.F. Slot J.W. Geuze H.J. Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway.Traffic. 2003; 4: 222-231Crossref PubMed Scopus (346) Google Scholar). However, it has also been reported that there are different classes of MVBs, some that fuse with lysosomes and others that give rise to exosomes (17Buschow S.I. Nolte-'t Hoen E.N.M. van Niel G. Pols M.S. ten Broeke T. Lauwen M. Ossendorp F. Melief C.J.M. Raposo G. Wubbolts R. et al.MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways.Traffic. 2009; 10: 1528-1542Crossref PubMed Scopus (293) Google Scholar). In this review, we will discuss the available information about the lipid composition of exosomes, including both lipid classes and lipid species. In addition, methodological issues related to the study of exosomal lipids will be discussed. Finally, the role of ether lipids and phosphoinositides (PIPs) in exosome biology will be presented. A caveat of exosome research is that the field has developed exponentially during the last decade without having a clear consensus on the optimal methodological approaches. This has caused confusion in the scientific community and, in some cases, results might have been misinterpreted or are based on unsatisfactory purification methods. In this section, these issues are briefly commented on in the context of exosomal lipids, and we refer to our recent review for a more extensive discussion about this topic (18Skotland T. Sandvig K. Llorente A. Lipids in exosomes: current knowledge and the way forward.Prog. Lipid Res. 2017; 66: 30-41Crossref PubMed Scopus (566) Google Scholar). Based on the studies published so far, exosomes are constituted to a large extent of membrane lipids, although it is possible that minor amounts of other lipids are captured from the cytosol during the formation of ILVs. The exosomal lipid composition should therefore normally be in agreement with the composition of a lipid bilayer. It is well-established that there is an asymmetric distribution of lipid classes in the two leaflets of the plasma membrane. Thus, sphingolipids and phosphatidylcholine (PC) are mostly present in the outer leaflet, and the other lipid classes are mainly located in the inner leaflet (19van Meer G. Voelker D.R. Feigenson G.W. Membrane lipids: where they are and how they behave.Nat. Rev. Mol. Cell Biol. 2008; 9: 112-124Crossref PubMed Scopus (4481) Google Scholar). One should expect a similar asymmetry in exosomal membranes, at least shortly after exosomes are released from cells. Thus, at least in mammalian cells, quantitative lipid analyses can be used to estimate whether the reported lipid data are in agreement with small vesicles with a bilayer structure. In contrast to exosomes, some EVs in human semen have been reported to contain internal membranes (20Höög J.L. Lötvall J. Diversity of extracellular vesicles in human ejaculates revealed by cryo-electron microscopy.J. Extracell. Vesicles. 2015; 4: 28680Crossref PubMed Scopus (112) Google Scholar), which may complicate such analysis. Recently, several articles have been published describing errors and limitations in lipidomic analyses and how they can be improved (21Simons K. How can omic science be improved?.Proteomics. 2018; 18: e1800039Crossref PubMed Scopus (19) Google Scholar, 22Wood P.L. Cebak J.E. Lipidomics biomarker studies: errors, limitations, and the future.Biochem. Biophys. Res. Commun. 2018; Crossref Scopus (14) Google Scholar). It was stressed that fatty acyl groups with an odd number of carbon atoms are present in limited amounts in cells, and data reporting large amounts of such fatty acyl groups should be interpreted with caution (22Wood P.L. Cebak J.E. Lipidomics biomarker studies: errors, limitations, and the future.Biochem. Biophys. Res. Commun. 2018; Crossref Scopus (14) Google Scholar). Several studies have reported high levels of cholesteryl ester (CE), triacylglycerol (TAG), and cardiolipin in exosomal preparations. CE and TAG are normally found in the core of lipid droplets (19van Meer G. Voelker D.R. Feigenson G.W. Membrane lipids: where they are and how they behave.Nat. Rev. Mol. Cell Biol. 2008; 9: 112-124Crossref PubMed Scopus (4481) Google Scholar) and cardiolipin in the inner membrane of mitochondria (23Daum G. Lipids of mitochondria.Biochim. Biophys. Acta. 1985; 822: 1-42Crossref PubMed Scopus (705) Google Scholar, 24Horvath S.E. Daum G. Lipids of mitochondria.Prog. Lipid Res. 2013; 52: 590-614Crossref PubMed Scopus (526) Google Scholar). Therefore, high levels of these lipids in exosome preparations may indicate that lipid droplets, lipoproteins, or mitochondria have been co-isolated with exosomes. Lipid droplets and mitochondria could potentially be leaked into the extracellular medium and later be co-isolated with exosomes if, during the time exosomes are allowed to accumulate in the medium, some cells die and their membrane is broken. In addition, both organelles can be included in autophagic vesicles (25Khaldoun S.A. Emond-Boisjoly M.A. Chateau D. Carriere V. Lacasa M. Rousset M. Demignot S. Morel E. Autophagosomes contribute to intracellular lipid distribution in enterocytes.Mol. Biol. Cell. 2014; 25: 118-132Crossref PubMed Scopus (74) Google Scholar), secreted by secretory autophagy, and eventually co-isolated with exosomes during the isolation process (26Hessvik N.P. Øverbye A. Brech A. Torgersen M.L. Jakobsen I.S. Sandvig K. Llorente A. PIKfyve inhibition increases exosome release and induces secretory autophagy.Cell. Mol. Life Sci. 2016; 73: 4717-4737Crossref PubMed Scopus (143) Google Scholar). A combination of lipidomic and proteomic analysis can provide interesting information about the origin of the different types of vesicles that are present in EV preparations. However, there is certainly a need for better methods to purify and characterize the different types of EVs (18Skotland T. Sandvig K. Llorente A. Lipids in exosomes: current knowledge and the way forward.Prog. Lipid Res. 2017; 66: 30-41Crossref PubMed Scopus (566) Google Scholar, 27Théry C. Amigorena S. Raposo G. Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids.Curr. Protoc. Cell Biol. 2006; Chapter 3: Unit 3.22PubMed Google Scholar, 28Coumans F.A.W. Brisson A.R. Buzas E.I. Dignat-George F. Drees E.E.E. El-Andaloussi S. Emanueli C. Gasecka A. Hendrix A. Hill A.F. et al.Methodological guidelines to study extracellular vesicles.Circ. Res. 2017; 120: 1632-1648Crossref PubMed Scopus (548) Google Scholar, 29Ramirez M.I. Amorim M.G. Gadelha C. Milic I. Welsh J.A. Freitas V.M. Nawaz M. Akbar N. Couch Y. Makin L. et al.Technical challenges of working with extracellular vesicles.Nanoscale. 2018; 10: 881-906Crossref PubMed Google Scholar). When reviewing the literature, it is difficult to evaluate the purity of the exosome preparations and, in this review, some studies where lipid analyses reveal the presence of lipids not expected to be present in exosomes, the plasma membrane, or endosomal membranes are commented on. It is important to include as much quantitative lipid data as possible in the articles. Lipid amounts are often given as nanomoles per milligram or as mole percent of total lipids and, preferably, both values should be reported. The use of mole percent has, in fact, some advantages, as it eliminates uncertainties in the measurement of protein concentrations that may occur by using, for example, different standard proteins or methods for protein analyses. Furthermore, in order to evaluate the importance of a specific treatment, the amount of the different lipids should be provided, not just the percent changes from cells to exosomes. Finally, in terms of studies of exosome biogenesis and release, it should be considered that there may be cell type-dependent regulatory mechanisms for the biogenesis and release of exosomes. For example, Trajokovic et al. (30Trajkovic K. Hsu C. Chiantia S. Rajendran L. Wenzel D. Wieland F. Schwille P. Brugger B. Simons M. Ceramide triggers budding of exosome vesicles into multivesicular endosomes.Science. 2008; 319: 1244-1247Crossref PubMed Scopus (2285) Google Scholar) reported that inhibition or siRNA-mediated depletion of neutral SMase, an enzyme that generates ceramide (Cer) from SM, resulted in reduced secretion of exosomes from Oli-neu cells. Later, a similar effect of neutral SMase was reported in the human embryonic kidney cell line, HEK293 (31Kosaka N. Iguchi H. Yoshioka Y. Takeshita F. Matsuki Y. Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells.J. Biol. Chem. 2010; 285: 17442-17452Abstract Full Text Full Text PDF PubMed Scopus (1503) Google Scholar), and in T-cells (32Mittelbrunn M. Gutierrez-Vazquez C. Villarroya-Beltri C. Gonzalez S. Sanchez-Cabo F. Gonzalez M.A. Bernad A. Sanchez-Madrid F. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells.Nat. Commun. 2011; 2: 282Crossref PubMed Scopus (1314) Google Scholar). However, the action of neutral SMase does not seem to be required for exosome release in all cell lines tested (33van Niel G. Charrin S. Simoes S. Romao M. Rochin L. Saftig P. Marks M.S. Rubinstein E. Raposo G. The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis.Dev. Cell. 2011; 21: 708-721Abstract Full Text Full Text PDF PubMed Scopus (550) Google Scholar, 34Phuyal S. Hessvik N.P. Skotland T. Sandvig K. Llorente A. Regulation of exosome release by glycosphingolipids and flotillins.FEBS J. 2014; 281: 2214-2227Crossref PubMed Scopus (125) Google Scholar). Furthermore, different MVB subtypes within a single cell line might exploit different pathways, as shown for syntenin-containing exosomes released from MCF-7 cells (35Ghossoub R. Lembo F. Rubio A. Gaillard C.B. Bouchet J. Vitale N. Slavik J. Machala M. Zimmermann P. Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2.Nat. Commun. 2014; 5: 3477Crossref PubMed Scopus (328) Google Scholar). The lipid composition of exosomes described in 10 studies as well as the enrichment factors from cells to exosomes in 8 of them are shown in Table 1. Interestingly, these studies show a two to three times enrichment from cells to exosomes of CHOL, SM, glycosphingolipids, and phosphatidylserine (PS). In general, these data show a similar mole percent of phosphatidylethanolamine (PE) in cells and exosomes, and a lower mole percent of PC and PI in exosomes than in their parent cells. Some years ago, we published an extensive quantitative lipid analysis of PC-3 cells and their exosomes (36Llorente A. Skotland T. Sylvänne T. Kauhanen D. Rog T. Orłowski A. Vattulainen I. Ekroos K. Sandvig K. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells.Biochim. Biophys. Acta. 2013; 1831: 1302-1309Crossref PubMed Scopus (463) Google Scholar). The relative changes for 22 lipid classes are shown in (Fig. 2), and the quantitative data for 14 of them are shown in the first column of Table 1. Another study of prostate cell lines, including PC-3 cells, also shows a similar enrichment of sphingolipids from cells to exosomes, but the phospholipid classes were grouped together making it difficult to compare these data with other studies (37Hosseini-Beheshti E. Pham S. Adomat H. Li N. Tomlinson Guns E.S. Exosomes as biomarker enriched microvesicles: characterization of exosomal proteins derived from a panel of prostate cell lines with distinct AR phenotypes.Mol. Cell. Proteomics. 2012; 11: 863-885Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar). Moreover, a lipidomic study of PC-3 cells treated with a precursor (hexadecylglycerol) of ether phospholipids has also been performed. Although this treatment resulted in major changes in the lipidome of cells and their exosomes, similar enrichment factors were obtained from cells to exosomes in cells treated with hexadecylglycerol compared with untreated cells (36Llorente A. Skotland T. Sylvänne T. Kauhanen D. Rog T. Orłowski A. Vattulainen I. Ekroos K. Sandvig K. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells.Biochim. Biophys. Acta. 2013; 1831: 1302-1309Crossref PubMed Scopus (463) Google Scholar, 38Phuyal S. Skotland T. Hessvik N.P. Simolin H. Øverbye A. Brech A. Parton R.G. Ekroos K. Sandvig K. Llorente A. The ether lipid precursor hexadecylglycerol stimulates the release and changes the composition of exosomes derived from PC-3 cells.J. Biol. Chem. 2015; 290: 4225-4237Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar), as shown in Table 1 and discussed in (18Skotland T. Sandvig K. Llorente A. Lipids in exosomes: current knowledge and the way forward.Prog. Lipid Res. 2017; 66: 30-41Crossref PubMed Scopus (566) Google Scholar). Lipidomic analysis of Oli-neu cells (30Trajkovic K. Hsu C. Chiantia S. Rajendran L. Wenzel D. Wieland F. Schwille P. Brugger B. Simons M. Ceramide triggers budding of exosome vesicles into multivesicular endosomes.Science. 2008; 319: 1244-1247Crossref PubMed Scopus (2285) Google Scholar) and HepG2/C3a cells (39Chapuy-Regaud S. Dubois M. Plisson-Chastang C. Bonnefois T. Lhomme S. Bertrand-Michel J. You B. Simoneau S. Gleizes P.E. Flan B. et al.Characterization of the lipid envelope of exosome encapsulated HEV particles protected from the immune response.Biochimie. 2017; 141: 70-79Crossref PubMed Scopus (91) Google Scholar) showed many similarities with PC-3 cells, although Oli-neu cells showed less enrichment of SM and a much higher enrichment of Cer in exosomes (Table 1). Because these studies did not include the CHOL content as percent of total lipids, we have, for comparison, assumed that it constituted 43 mol%, i.e., the same level as in other exosome preparations listed in Table 1.TABLE 1.Lipid composition of exosomes released by individual cell typesLipidsPC-3 Cells (36Llorente A. Skotland T. Sylvänne T. Kauhanen D. Rog T. Orłowski A. Vattulainen I. Ekroos K. Sandvig K. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells.Biochim. Biophys. Acta. 2013; 1831: 1302-1309Crossref PubMed Scopus (463) Google Scholar)PC-3 Cells + HG (38Phuyal S. Skotland T. Hessvik N.P. Simolin H. Øverbye A. Brech A. Parton R.G. Ekroos K. Sandvig K. Llorente A. The ether lipid precursor hexadecylglycerol stimulates the release and changes the composition of exosomes derived from PC-3 cells.J. Biol. Chem. 2015; 290: 4225-4237Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar)Oli-neu Cells (30Trajkovic K. Hsu C. Chiantia S. Rajendran L. Wenzel D. Wieland F. Schwille P. Brugger B. Simons M. Ceramide triggers budding of exosome vesicles into multivesicular endosomes.Science. 2008; 319: 1244-1247Crossref PubMed Scopus (2285) Google Scholar)HepG2/C3a (39Chapuy-Regaud S. Dubois M. Plisson-Chastang C. Bonnefois T. Lhomme S. Bertrand-Michel J. You B. Simoneau S. Gleizes P.E. Flan B. et al.Characterization of the lipid envelope of exosome encapsulated HEV particles protected from the immune response.Biochimie. 2017; 141: 70-79Crossref PubMed Scopus (91) Google Scholar)B-Lymphocytes (40Wubbolts R. Leckie R.S. Veenhuizen P.T. Schwarzmann G. Möbius W. Hoernschemeyer J. Slot J.W. Geuze H.J. Stoorvogel W. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation.J. Biol. Chem. 2003; 278: 10963-10972Abstract Full Text Full Text PDF PubMed Scopus (699) Google Scholar)Mast Cells (41Laulagnier K. Motta C. Hamdi S. Roy S. Fauvelle F. Pageaux J.F. Kobayashi T. Salles J.P. Perret B. Bonnerot C. et al.Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization.Biochem. J. 2004; 380: 161-171Crossref PubMed Scopus (0) Google Scholar)Dendritic Cells (41Laulagnier K. Motta C. Hamdi S. Roy S. Fauvelle F. Pageaux J.F. Kobayashi T. Salles J.P. Perret B. Bonnerot C. et al.Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization.Biochem. J. 2004; 380: 161-171Crossref PubMed Scopus (0) Google Scholar)Reticulocytes (42Vidal M. Sainte-Marie J. Philippot J.R. Bienvenue A. Asymmetric distribution of phospholipids in the membrane of vesicles released during in vitro maturation of guinea pig reticulocytes: evidence precluding a role for "aminophospholipid translocase ".J. Cell. Physiol. 1989; 140: 455-462Crossref PubMed Scopus (109) Google Scholar)Platelets (45Pienimaeki-Roemer A. Kuhlmann K. Bottcher A. Konovalova T. Black A. Orso E. Liebisch G. Ahrens M. Eisenacher M. Meyer H.E. et al.Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets.Transfusion. 2015; 55: 507-521Crossref PubMed Scopus (84) Google Scholar)Adipocytes (46Durcin M. Fleury A. Taillebois E. Hilairet G. Krupova Z. Henry C. Truchet S. Trotzmuller M. Kofeler H. Mabilleau G. et al.Characterisation of adipocyte-derived extracellular vesicle subtypes identifies distinct protein and lipid signatures for large and small extracellular vesicles.J. Extracell. Vesicles. 2017; 6: 1305677Crossref PubMed Scopus (123) Google Scholar)%Factor%Factor%aPercent CHOL not reported; CHOL set to 43% to better compare the content of other lipid classes with the other data shown.Factor%aPercent CHOL not reported; CHOL set to 43% to better compare the content of other lipid classes with the other data shown.Factor%Factor%bRecalculated from their data.Factor%bRecalculated from their data.,cCHOL not reported; the sum for the other lipid classes is 100% (including LysoPC not included in this table).Factor%Factor%%aPercent CHOL not reported; CHOL set to 43% to better compare the content of other lipid classes with the other data shown.CHOL43.52.3591.7432.3431.942.13.0151.0NRNR471.0342.543SM16.32.49.12.08.21.59.710.823.02.3dSum of SM and the glycosphingolipid, GM3.122.8202.28.4dSum of SM and the glycosphingolipid, GM3.1.3112.512.5PC15.30.3110.80.3326.70.67200.67(20.3)eSum for all classes shown in parentheses and having the same numbers.(0.76)eSum for all classes shown in parentheses and having the same numbers.280.66260.623.51.0315.933PS11.72.16.91.214.93.015.62.4(20.3)eSum for all classes shown in parentheses and having the same numbers.(0.76)eSum for all classes shown in parentheses and having the same numbers.(16)eSum for all classes shown in parentheses and having the same numbers.(1.2)eSum for all classes shown in parentheses and having the same numbers.(19)eSum for all classes shown in parentheses and having the same numbers.(1.6)eSum for all classes shown in parentheses and having the same numbers.5.90.9210.51.1PE5.80.551.10.2110.91.07.41.2(14.6)eSum for all classes shown in parentheses and having the same numbers.(0.7)eSum for all classes shown in parentheses and having the same numbers.241.08261.1312.70.843.14.0PE ethers3.31.24.70.81(14.6)eSum for all classes shown in parentheses and having the same numbers.(0.7)eSum for all classes shown in parentheses and having the same numbers.3.2DAG1.51.51.10.920.8PC ethers0.810.400.70.281.4PG0.170.170.10.07NRPA0.161.80.10.33(20.3)eSum for all classes shown in parentheses and having the same numbers.(0.76)eSum for all classes shown in parentheses and having the same numbers.NRPI0.130.130.30.16NR4.10.18(20.3)eSum for all classes shown in parentheses and having the same numbers.(0.76)eSum for all classes shown in parentheses and having the same numbers.(16)eSum for all classes shown in parentheses and having the same numbers.(1.2)eSum for all classes shown in parentheses and having the same numbers.(19)eSum for all classes shown in parentheses and having the same numbers.(1.6)eSum for all classes shown in parentheses and having the same numbers.2.41.15.22.3Cer0.321.30.71.2NR3.30.632.00.400.2HexCer0.763.82.32.12.00.02LacCer0.123.0fEnrichments of other lipid classes are shown in Fig. 2.0.71.8NRLipid analysisMSMSMSNRMS/GCTLCTLC/GLCTLC/GLCTLCMSMSExosome preparationsgExosome preparations: methods used to isolate the exosome preparations.SFM + SUCSFM + SUCSFM + SUC + SGuFCS + SUC + IGuFCS+ SUC+ SG + immunocaptureuFCS + SUCuFCS + SUCuFCS + SUCSUC + IGSFM + SUC%, percent of total lipid quantified; Factor, factor of enrichment from cells to exosomes; DAG, diacylglycerol; NR, not reported; LacCer, lactosylceramide; PA, phosphatidic acid; PG, phosphatidylglycerol; SFM, serum free medium; uFCS, ultracentrifuged FCS; SUC, sequential centrifugation; SG, sucrose gradient; IG, iodixanol gradient.a Percent CHOL not reported; CHOL set to 43% to better compare the content of other lipid classes with the other data shown.b Recalculated from their data.c CHOL not reported; the sum for the other lipid classes is 100% (including LysoPC not included in this table).d Sum of SM and the glycosphingolipid, GM3.e Sum for all classes shown in parentheses and having the same numbers.f Enrichments of other lipid classes are shown in Fig. 2.g Exosome preparations: methods used to isolate the exosome preparations. Open table in a new tab %, percent of total lipid quantified; Factor, factor of enrichment from cells to exosomes; DAG, diacylglycerol; NR, not reported; LacCer, lactosylceramide; PA, phosphatidic acid; PG, phosphatidylglycerol; SFM, serum free medium; uFCS, ultracentrifuged FCS; SUC, sequential centrifugation; SG, sucrose gradient; IG, iodixanol gradient. In the studies discussed above, MS
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