Title : Fatty acid chain length drives lysophosphatidylserine-dependent immunological outputs - Khandelwal_2021_Cell.Chem.Biol__ |
Author(s) : Khandelwal N , Shaikh M , Mhetre A , Singh S , Sajeevan T , Joshi A , Balaji KN , Chakrapani H , Kamat SS |
Ref : Cell Chemical Biology , : , 2021 |
Abstract :
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. |
PubMedSearch : Khandelwal_2021_Cell.Chem.Biol__ |
PubMedID: 33571455 |
Gene_locus related to this paper: human-ABHD12 |
Gene_locus | human-ABHD12 |
Family | ABHD12-PHARC |
Khandelwal N, Shaikh M, Mhetre A, Singh S, Sajeevan T, Joshi A, Balaji KN, Chakrapani H, Kamat SS (2021)
Fatty acid chain length drives lysophosphatidylserine-dependent immunological outputs
Cell Chemical Biology
:
Khandelwal N, Shaikh M, Mhetre A, Singh S, Sajeevan T, Joshi A, Balaji KN, Chakrapani H, Kamat SS (2021)
Cell Chemical Biology
: