Oxygenated fatty acids in plasma of tumor-bearing animals stimulate their scavenger receptor A1-mediatd uptake by dendritic cells: mass-spectrometric evidence

Details

• Personal Author:
  Cao W ; Gabrilovich DI ; Kagan VE ; Tyurin VA ; Tyurina Y
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Antigens Carcinogens Cytology Cytotoxins Immune System Laboratories Lipids Mass Spectrometry Neoplasms Occupational Health Safety

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• Keywords:
  Cancer Cell-alteration Cell-damage Cellular-reactions Cellular-transport-mechanism Cellular-uptake Cytotoxic-effects Fatty-acids Immune-reaction Immune-system In-vitro-study Laboratory-animals Mass-spectrometry Oxidation Oxidative-processes Tumorigens Tumors

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; Florida ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 9 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  351-352
• Volume:
  126
• NIOSHTIC Number:
  nn:20040656
• Citation:
  Toxicologist 2012 Mar; 126(Suppl 1):351-352
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
• Supplement:
  1
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b870dbefdc88d4295af2bc0d87fa7a11f9c0890d538851fb82145a9b46c73195706eed7a84c01a6fa74a6a11ddb2aef89d94e3265d5d2f0fb4212c2398fd389e
• Download URL:
  https://stacks.cdc.gov/view/cdc/193446/cdc_193446_DS1.pdf
• File Type:
  [PDF - 487.46 KB ]