title: Stearoyl lysophosphatidylcholine enhances the phagocytic ability of macrophages through the AMP-activated protein kinase/p38 mitogen activated protein kinase pathway.
abstract: 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.
authors: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Hui
authors: H
authors: Quan
authors: Division of Hepatico-Biliary-Pancreatic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Young-Hoe
authors: YH
authors: Hur
authors: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Chun
authors: C
authors: Xin
authors: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Joung-Min
authors: JM
authors: Kim
authors: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Jeong-Il
authors: JI
authors: Choi
authors: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Man-Young
authors: MY
authors: Kim
authors: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea. Electronic address: nextphil2@jnu.ac.kr.
authors: Hong-Beom
authors: HB
authors: Bae
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004926:Escherichia coli / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000008:administration & dosage*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D008244:Lysophosphatidylcholines; D011725:Pyridines; D034741:RNA, Small Interfering; C026564:stearoyl alpha-lysolecithin; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; C093642:SB 203580
keywords: AMP-activated protein kinase; Macrophage; Phagocytosis; Stearoyl lysophosphatidylcholine; p38 mitogen-activated protein kinase