Bioactive products generated by group V sPLA(2) hydrolysis of LDL activate macrophages to secrete pro-inflammatory cytokines

Cytokine. 2010 Apr;50(1):50-7. doi: 10.1016/j.cyto.2009.12.009. Epub 2010 Feb 6.


Objective: Previous studies have established that hydrolysis of LDL by Group V secretory phospholipase A(2) (GV sPLA(2)) generates a modified particle capable of inducing macrophage foam cell formation. The aim of the present study was to determine whether GV sPLA(2)-hydrolyzed LDL (GV-LDL) produces pro-atherogenic effects in macrophages independent of cholesterol accumulation.

Methods and results: J-774 cells incubated with GV-LDL produced more TNF-alpha and IL-6 compared to cells incubated with control-LDL. Indirect immunofluorescence showed that GV-LDL but not control-LDL induced nuclear translocation of NFkappaB. Inhibitors of NFkappaB activation, effectively blocked cytokine production induced by GV-LDL. Control-LDL and GV-LDL were separated from albumin present in reaction mixtures by ultracentrifugation. The albumin fraction derived from GV-LDL contained 80% of the FFA generated and was more potent than the re-isolated GV-LDL in inducing pro-inflammatory cytokine secretion. Linoleic acid (18:2) and oleic acid (18:1) were the most abundant FFAs generated, whereas newly formed lyso-PCs contained 14:0 (myristic), 16:1 (palmitic), and 18:2 fatty acyl groups. Experiments with synthetic FFA showed that 18:1 induced J-774 cells to secrete TNF-alpha and IL-6.

Conclusions: These results indicate that in addition to promoting atherosclerotic lipid accumulation in macrophages, GV sPLA(2) hydrolysis of LDL leads to activation of NFkappaB, a key regulator of inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Albumins / metabolism
  • Animals
  • COS Cells
  • Cell Nucleus / metabolism
  • Chlorocebus aethiops
  • Cholesterol, LDL / metabolism*
  • Fatty Acids / metabolism
  • Group V Phospholipases A2 / metabolism*
  • Humans
  • Hydrolysis
  • Inflammation Mediators / metabolism*
  • Interleukin-6 / metabolism*
  • Lipolysis
  • Macrophage Activation*
  • Macrophages / metabolism*
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • Protein Binding
  • Protein Transport
  • Tumor Necrosis Factor-alpha / metabolism*


  • Albumins
  • Cholesterol, LDL
  • Fatty Acids
  • Inflammation Mediators
  • Interleukin-6
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Group V Phospholipases A2