| First Author | Khandelwal N | Year | 2021 |
| Journal | Cell Chem Biol | Volume | 28 |
| Issue | 8 | Pages | 1169-1179.e6 |
| PubMed ID | 33571455 | Mgi Jnum | J:347783 |
| Mgi Id | MGI:7625814 | Doi | 10.1016/j.chembiol.2021.01.008 |
| Citation | Khandelwal N, et al. (2021) Fatty acid chain length drives lysophosphatidylserine-dependent immunological outputs. Cell Chem Biol 28(8):1169-1179.e6 |
| abstractText | In humans, lysophosphatidylserines (lyso-PSs) are potent lipid regulators of important immunological processes. Given their structural diversity and commercial paucity, here we report the synthesis of methyl esters of lyso-PS (Me-lyso-PSs) containing medium- to very-long-chain (VLC) lipid tails. We show that Me-lyso-PSs are excellent substrates for the lyso-PS lipase ABHD12, and that these synthetic lipids are acted upon by cellular carboxylesterases to produce lyso-PSs. Next, in macrophages we demonstrate that VLC lyso-PSs orchestrate pro-inflammatory responses and in turn neuroinflammation via a Toll-like receptor 2 (TLR2)-dependent pathway. We also show that long-chain (LC) lyso-PSs robustly induce intracellular cyclic AMP production, cytosolic calcium influx, and phosphorylation of the nodal extracellular signal-regulated kinase to regulate macrophage activation via a TLR2-independent pathway. Finally, we report that LC lyso-PSs potently elicit histamine release during the mast cell degranulation process, and that ABHD12 is the major lyso-PS lipase in these immune cells. |
