Stearoyl lysophosphatidylcholine enhances the phagocytic ability of macrophages through the AMP-activated protein kinase/p38 mitogen activated protein kinase pathway.
A previous study showed that stearoyl lysophosphatidylcholine (sLPC) suppressed extracellular high mobility group box 1 translocation in macrophages stimulated with lipopolysaccharide through AMP-activated protein kinase (AMPK) activation. In the present study, we investigated whether sLPC-induced AMPK activation could enhance macrophages phagocytosis of bacteria. We found that sLPC increased phosphorylation of AMPK and acetyl-CoA carboxylase, a downstream target of AMPK, in a time- and dose-dependent manner in macrophages. Furthermore, sLPC increased the uptake of FITC-conjugated Escherichia coli by macrophages in a dose-dependent manner, and treatment with an AMPK inhibitor (compound C) or siRNA to AMPKα1 reversed this uptake. sLPC increased the phosphorylation of p38 mitogen-activated protein kinase (MAPK), but inhibition of AMPK activity with compound C or siRNA to AMPKα1 prevented the sLPC-induced increase in p38 MAPK phosphorylation. SB203580, a p38 MAPK inhibitor, decreased sLPC-induced phagocytosis. In vivo, systemic administration of sLPC to mice led to increased AMPK and p38 MAPK activity in the lung and to increased phagocytosis of fluorescent E. coli in bronchoalveolar lavage cells. These results suggest that sLPC increases macrophages phagocytosis through activation of the AMPK/p38 MAPK pathway. Therefore, sLPC is a candidate pharmacological agent for the treatment of bacterial infections in clinically relevant conditions.
['Quan|Hui|H|', 'Hur|Young-Hoe|YH|', 'Xin|Chun|C|', 'Kim|Joung-Min|JM|', 'Choi|Jeong-Il|JI|', 'Kim|Man-Young|MY|', 'Bae|Hong-Beom|HB|']
D055372:AMP-Activated Protein Kinases D000818:Animals D004926:Escherichia coli D007093:Imidazoles D008244:Lysophosphatidylcholines D017737:Macrophages, Peritoneal D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D010587:Phagocytosis D010766:Phosphorylation D011725:Pyridines D000067996:RAW 264.7 Cells D034741:RNA, Small Interfering D015398:Signal Transduction D048051:p38 Mitogen-Activated Protein Kinases
Stearoyl lysophosphatidylcholine Macrophage AMP-activated protein kinase Phagocytosis p38 mitogen-activated protein kinase