Parenteral medium-chain triglyceride-induced neutrophil activation is not mediated by a Pertussis Toxin sensitive receptor

Background & aims: Lipid-induced immune modulation might contribute to the increased infection rate that is observed in patients using parenteral nutrition. We previously showed that emulsions containing medium-chain triglycerides (LCT/MCTs or pure MCTs), but not pure long-chain triglycerides (LCTs), impair neutrophil functions, modulate cell-signaling and induce neutrophil activation in vitro. It has recently been shown that medium-chain fatty acids are ligands for GPR84, a pertussis toxin (PT)sensitive G-protein-coupled receptor (GPCR). This finding urged LIS to investigate whether MCT-induced neutrophil activation is mediated by PT-sensitive GPCRs. Methods: Neutrophils isolated from blood of healthy volunteers were pre-incubated with FT (0.5-1 mu g/mL, 1.5 h) and analyzed for the effect of this pre-incubation on LCT/MCT (2.5 mmol/L)-dependent modulation of serum-treated zymosan (STZ)-induced intracellular Ca2+ mobilization and on LCT/MCT (5 mmol/L)-induced expression of cell Surface adhesion (CD11b) and degranulation (CD66b) markets and oxygen radical (ROS) production. Results: PT did not inhibit the effects of LCT/MCT on the STZ-induced increase in cytosolic free Ca2+ concentration. LCT/MCT increased ROS production to 146% Of unstimulated cells. However, pre-incubation with PT did not inhibit the LCT/MCT-induced ROS production. Furthermore, the LCT/MCT-induced increase in CD11b and CD66b expression (196% and 235% of unstimulated cells, respectively) was not inhibited by pre-incubation with PT. Conclusion: LCT/MCT-induced neutrophil activation does not involve the action of a PT-sensitive G-protein-COLI pled receptor. (c) 2008 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.