Oxygenated fatty acids in plasma of tumor-bearing animals stimulate their scavenger receptor A1-mediatd uptake by dendritic cells: mass-spectrometric evidence.
Cao-W; Tyurin-VA; Tyurina-Y; Gabrilovich-DI; Kagan-VE
Toxicologist 2012 Mar; 126(Suppl 1):351-352
Dendritic cells (DC) are the most potent antigen presenting cells responsible for the development of immune responses in cancer. The function of DC in tumor-bearing hosts is severely compromised. To a large extent, the defects in DC function in tumor-bearing mice and patients with cancer are due to the accumulation of high amounts of lipids. To identify possible sources of lipids taken-up by the DC, we performed oxidative lipidomics analysis of plasma and DC of tumor-bearing animals. We found that both plasma and DC contained significant amounts of highly oxidizable polyunsaturated free fatty acids (FFA) represented mostly by C18:2, C18:3, C20:4 and C22:6 species as well as their oxygenated (oxFFA) species. Their contents were significantly higher in EL-4 tumor-bearing animals than in control mice. MS analysis revealed that oxFFA were mainly represented by 13-HODE, 9- HODE, 12-HETE, tetranor-12-HETE, and 16-HDoHE. To determine the extent to which scavenger receptor A1 might be involved in the uptake and intracellular transport of oxFFA we assessed their content in DC generated from wt and Msr1-/- HPC in vitro. Markedly reduced levels of all four characterized oxFFA were found in DC from k/o mice vs those detected in wt animals. Further, we estimated whether oxFFA in DC were esterified into the most abundant class of neutral lipids accumulating in DC of EL-4 tumor-bearing animals, triglycerides (TG). We found that oxTG species containing HODE and corresponding to C16:1/C18:2-OH/C15:0 was present only in DC from tumor-bearing mice. Thus, we suggest that the presence of oxygenated species of lipids in plasma of EL-4 tumor-bearing animals may be responsible for their uptake by DC possibly resulting in the loss of their immuno-surveillance function.
Cytology; Cytotoxic-effects; Cell-alteration; Cell-damage; Cellular-reactions; Cancer; Tumorigens; Tumors; Fatty-acids; Antigens; Immune-reaction; Immune-system; Lipids; Oxidative-processes; Laboratory-animals; Mass-spectrometry; Cellular-uptake; Oxidation; Cellular-transport-mechanism; In-vitro-study
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
University of Pittsburgh at Pittsburgh