title: Endotoxin-induced autocrine ATP signaling inhibits neutrophil chemotaxis through enhancing myosin light chain phosphorylation.
abstract: Although the neutrophil recruitment cascade during inflammation has been well described, the molecular players that halt neutrophil chemotaxis remain unclear. In this study, we found that lipopolysaccharide (LPS) was a potent stop signal for chemotactic neutrophil migration. Treatment with an antagonist of the ATP receptor (P2X1) in primary human neutrophils or knockout of the P2X1 receptor in neutrophil-like differentiated HL-60 (dHL-60) cells recovered neutrophil chemotaxis. Further observations showed that LPS-induced ATP release through connexin 43 (Cx43) hemichannels was responsible for the activation of the P2X1 receptor and the subsequent calcium influx. Increased intracellular calcium stopped neutrophil chemotaxis by activating myosin light chain (MLC) through the myosin light chain kinase (MLCK)-dependent pathway. Taken together, these data identify a previously unknown function of LPS-induced autocrine ATP signaling in inhibiting neutrophil chemotaxis by enhancing MLC phosphorylation, which provides important evidence that stoppage of neutrophil chemotaxis at infectious foci plays a key role in the defense against invading pathogens.
authors.affiliation: Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Weiting
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Yuyun
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Yisen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China; sunbinwe@hotmail.com.
authors.forename: Bingwei
authors.initials: B
authors.lastname: Sun
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D019898:Autocrine Communication; D002633:Chemotaxis / Q000502:physiology*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D018994:Myosin Light Chains / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*; D010766:Phosphorylation; D058474:Receptors, Purinergic P2X1; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018031:Connexin 43; D004731:Endotoxins; C500216:GJA1 protein, human; D008070:Lipopolysaccharides; D018994:Myosin Light Chains; D058474:Receptors, Purinergic P2X1; D000255:Adenosine Triphosphate
keywords: ATP; chemotaxis; endotoxin; myosin light chain; neutrophil