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

详细信息    查看全文

• 作者：Michelle W.J. Versleijen ; Joantine C.J. van Esterik ; Hennie M.J. Roelofs ; Sjenet E. van Emst-de Vries ; Peter H.G.M. Willems ; Geert J.A. Wanten
• 关键词：Parenteral ; Medium-chain triglycerides ; Neutrophil ; Human ; Immune modulation ; G-protein-coupled receptor
• 刊名：Clinical Nutrition
• 出版年：2009
• 出版时间：February 2009
• 年：2009
• 卷：28
• 期：1
• 页码：59-64
• 全文大小：361 K

文摘

Summary

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 us 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 PT (0.5–1 μg/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) markers 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-coupled receptor.