title: Autotaxin and Endotoxin-Induced Acute Lung Injury.
abstract: Acute Lung Injury (ALI) is a life-threatening, diffuse heterogeneous lung injury characterized by acute onset, pulmonary edema and respiratory failure. Lipopolysaccharide (LPS) is a common cause of both direct and indirect lung injury and when administered to a mouse induces a lung phenotype exhibiting some of the clinical characteristics of human ALI. Here, we report that LPS inhalation in mice results in increased bronchoalveolar lavage fluid (BALF) levels of Autotaxin (ATX, Enpp2), a lysophospholipase D largely responsible for the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA) in biological fluids and chronically inflamed sites. In agreement, gradual increases were also detected in BALF LPA levels, following inflammation and pulmonary edema. However, genetic or pharmacologic targeting of ATX had minor effects in ALI severity, suggesting no major involvement of the ATX/LPA axis in acute inflammation. Moreover, systemic, chronic exposure to increased ATX/LPA levels was shown to predispose to and/or to promote acute inflammation and ALI unlike chronic inflammatory pathophysiological situations, further suggesting a differential involvement of the ATX/LPA axis in acute versus chronic pulmonary inflammation.
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece.
authors.forename: Marios-Angelos
authors.initials: MA
authors.lastname: Mouratis
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece.
authors.forename: Christiana
authors.initials: C
authors.lastname: Magkrioti
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece.
authors.forename: Nikos
authors.initials: N
authors.lastname: Oikonomou
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece.
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Katsifa
authors.affiliation: Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Prestwich
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece.
authors.forename: Eleanna
authors.initials: E
authors.lastname: Kaffe
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Aidinis
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D008070:Lipopolysaccharides / Q000633:toxicity; D008246:Lysophospholipids / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D000099189:Lysophospholipase D
chemical_list: D008070:Lipopolysaccharides; D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid