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

Description

Exosomes are bioactive vesicles released from multivesicular bodies by intact cells and participate in intercellular signalling. 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 PLD / PAP1 pathway leading to the formation of diglycerides. RBL-2H3 exosomes also carried members of the three phospholipase A2 classes, i.e. the calcium-dependent cPLA2-IVA, the calcium-independent iPLA2-VIA and the secreted sPLA2-IIA and V. Remarkably, almost all members of the Ras GTPase superfamily were present, and incubation of exosomes with GTPgammaS triggered activation of PLA2s and PLD2. A large panel of free fatty acids, including arachidonic acid, and derivatives such as prostaglandin E2 and 15-deoxy-Delta12,14-prostaglandinJ2 were detected. We observed that the exosomes were internalized by resting and activated RBLcells, 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.

Abstract

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