Table 5.
Functional role for EVs in alcohol-induced liver injury.
| Model/EV source | Dose (EtOH) | Isolation method | EV marker | Result | References [#] |
|---|---|---|---|---|---|
| HepG2ADH HepG2CYP2E1 Cell media |
100 mmol/L Collected 24 h later | 110,000 g UC | TSG101/CD63/LAMP1/RAB5 | Increased EVs in HepG2CYP2E1 but not HepG2ADH. CYP2E1 inhibitor prevents increase in EV release | [161] |
| Fischer F344 Plasma | Three oral doses of 6 g/kg | Exoquick (commercial) | CD63 | Increased EVs and CYP enzymes (CYP2E1) packaged into Alc-EVs. Suggests Alc-EVs mediate injury through CYP2E1 | |
| Alcoholic Patients Plasma | – | [160] | |||
| Fischer F344a Plasmab | Three oral doses of 6 g/kg | Exoquick (commercial) | CD63 | In vitro: Alc-EVs added to PMH decrease cell viability, increase pJNK, and increase cleaved caspase 3 | [160] |
| HepRGb Monocytic cells (U1) Cell media | Alc-EVsc and 50 mmol/L EtOH | Exoquick (commercial) | CD63/CD81 | CYP2E1 knockdown prevents Alc toxicity but not Alc plus Alc-EV toxicity | [130] |
| Huh 7.5 PHH Cell media | 100 mmol/L (24, 48, 72 h) | Exoquick-TC (commercial) | CD63 | miRNA122 enriched in Alc-EVs. miRNA122 can be transferred from Alc-EVs to monocyte and modulate gene expression | [163] |
| THP-1 Monocytes Cell Media | 100 mmol/L (24, 48, 72 h) | Exoquick-TC (commercial) | CD63 | miRNA-27A enriched in Alc-EVs and can induce M2 polarization in naïve monocytes | [164] |
| HepG2 Cell Media | 100 mmol/L Collected 24 h later | 110,000 g UC | TSG101/CD63/LAMP1/RAB5 | Alc-EVs enriched in CD40L and located on exterior surface. In vitro and in vivo evidence for EV-CD40L macrophage activation | [161] |
| C57BL/6 Plasma | Liber DeCarli Diet (5% v/v) for 5 weeks | Exoquick-TC (commercial) | CD63 GRP-78 negative | Alc-EVs enriched in immune/inflammation pathways. Alc-EVs taken up by hepatocytes and Kupffer cells in naïve mice. Increased monocytic infiltration | [159] |
| RAW Macrophages Cell Media | Alcohol-EVs (50 μL at 50 μg/mL) | CD63 | Alc-EVs contain Hsp90 and activate macrophages. Hsp90 inhibitors prevent activation. Suggest Hsp90 mediates increased monocytic infiltration in vivo | [159] |
a
Study treated mice with three oral doses of 6 g/kg alcohol, collected EVs from plasma, and then took these alcohol-EVs and added to primary hepatocytes.
b
Does not mention concentration of EVs added.
c
Alc-EVs were collected from plasma of C57BL/6 mice that had been treated with one dose of Alc (5 g/kg).