Lipid droplets with oxygenated fatty acids and triglycerides in dendritic cells: possible role in antigen presentation in cancer.
Tyurin-V; Cao-W; Loomen-J; Kagan-V; Gabrilovich-D
Toxicologist 2013 Mar; 132(1):428
Immuno-surveillance plays a critical role in control of tumor progression whereby dendritic cells (DC) are the most potent antigen presenting cells responsible for the development of immune responses. Our previous work has identified lipid droplets as potent regulators of DC's immune functions. Notably, DCs isolated from tumor-bearing mice or treated with tumor explant supernatants (TES) accumulated lipid droplets containing considerable amounts of PUFA (C18:2, C18:3, C20:4 and C22:6). Among those, the amounts of C18:2 were significantly higher compared to other PUFA species. Since accumulation of lipid droplets in DCs in cancer was mediated via Msr1 receptor, which is primarily responsible for the uptake of oxidatively modified lipids, we performed analysis of oxidized lipids in DCs using LC-ESI-MS. To investigate possible role of oxidized fatty acid in antigen presentation we used a model system were DCs from na´ve mice were grown in the presence of C18:2. Treatment of DCs with C18:2 in combination with a hydrophobic free radical generator, an azo-intiator AMVN, - but not with C18:2 alone - resulted in accumulation of oxygenated lipid droplets and caused significant decrease in antigen presentation. Oxygenated FFA containing one, two and three oxygens as well as oxygenated triacylglycerols, TAGs, including truncated TAGs with m/z 766 [M+NH4]+, containing acyl corresponding to 9-oxo-nonanoic acid, were observed in DC grown in the presence of TES and DC treated with C18:2 and AMVN. Given that lipid droplets can directly co-localize with cellular compartments involved in antigen processing and formation of pMHC complexes, it is likely that accumulation of oxygenated FFAs and TAGs in DC may be responsible for the loss of their immune-regulatory functions in cancer.
Toxicology; Laboratory-animals; Cancer; Lipids; Fatty-acids; Cell-alteration; Cell-damage; Cellular-function; Cellular-reactions; Oxidative-processes; Antigens; Immune-reaction; Tumors; Genes; Free-radical-generation; Free-radicals; Azo-compounds; Glycerides
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas
University of Pittsburgh at Pittsburgh