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PMID: 20424270 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins.

Journal of lipid research ·Vol. 51 ·No. 8 ·2010-08-00 ·Pages 2105-20

Subra C, Grand D, Laulagnier K, Stella A, Lambeau G, Paillasse M, De Medina P, Monsarrat B, Perret B, Silvente-Poirot S, Poirot M, Record M

Abstract

Exosomes are bioactive vesicles released from multivesicular bodies (MVB) by intact cells and participate in intercellular signaling. We investigated the presence of lipid-related proteins and bioactive lipids in RBL-2H3 exosomes. Besides a phospholipid scramblase and a fatty acid binding protein, the exosomes contained the whole set of phospholipases (A2, C, and D) together with interacting proteins such as aldolase A and Hsp 70. They also contained the phospholipase D (PLD) / phosphatidate phosphatase 1 (PAP1) pathway leading to the formation of diglycerides. RBL-2H3 exosomes also carried members of the three phospholipase A2 classes: the calcium-dependent cPLA(2)-IVA, the calcium-independent iPLA(2)-VIA, and the secreted sPLA(2)-IIA and V. Remarkably, almost all members of the Ras GTPase superfamily were present, and incubation of exosomes with GTPgammaS triggered activation of phospholipase A(2) (PLA(2))and PLD(2). A large panel of free fatty acids, including arachidonic acid (AA) and derivatives such as prostaglandin E(2) (PGE(2)) and 15-deoxy-Delta(12,14)-prostaglandinJ(2) (15-d PGJ(2)), were detected. We observed that the exosomes were internalized by resting and activated RBL cells and that they accumulated in an endosomal compartment. Endosomal concentrations were in the micromolar range for prostaglandins; i.e., concentrations able to trigger prostaglandin-dependent biological responses. Therefore exosomes are carriers of GTP-activatable phospholipases and lipid mediators from cell to cell.

MeSH Terms
Biological Transport Cell Line Dinoprostone/metabolism Endosomes/metabolism Enzyme Activation/drug effects Exosomes/drug effects,metabolism Guanosine Triphosphate/pharmacology Humans Lipolysis Pancreatitis-Associated Proteins Phosphatidate Phosphatase/metabolism Phospholipase D/metabolism Phospholipases/metabolism Phospholipases A2/metabolism Prostaglandin D2/analogs & derivatives,metabolism Prostaglandins/metabolism Proteome/metabolism
Chemicals
Pancreatitis-Associated Proteins Prostaglandins Proteome REG3A protein, human 9-deoxy-delta-9-prostaglandin D2 Guanosine Triphosphate Phospholipases Phospholipases A2 Phosphatidate Phosphatase phospholipase D2 Phospholipase D Dinoprostone Prostaglandin D2
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Subra Caroline
Metabolism, Oncogenesis and Cell Differentiation Group, INSERM Research Center 563, Pathophysiology Center of Toulouse Purpan, Hôpital Purpan, Toulouse, France.
Grand David
Laulagnier Karine
Stella Alexandre
Lambeau Gérard
Paillasse Michael
De Medina Philippe
Monsarrat Bernard
Perret Bertrand
Silvente-Poirot Sandrine
Poirot Marc
Record Michel
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Article Info
Journal
Journal of lipid research
Abbr.
J Lipid Res
ISSN
1539-7262
DOI
10.1194/jlr.M003657
Published
2010-08-00
Epub
2010-00-27
Pages
2105-20
Language
English
Region
United States
NLM ID
0376606
PMCID
PMC2903822
Subset
IM
External Links
PubMed source DOI: 10.1194/jlr.M003657 PMC Full Text View journal details
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