title: Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs.
abstract: The extracellular lysophospholipase D autotaxin (ATX) and its product, lysophosphatidic acid, have diverse functions in development and cancer, but little is known about their functions in the immune system. Here we found that ATX had high expression in the high endothelial venules of lymphoid organs and was secreted. Chemokine-activated lymphocytes expressed receptors with enhanced affinity for ATX, which provides a mechanism for targeting the secreted ATX to lymphocytes undergoing recruitment. Lysophosphatidic acid induced chemokinesis in T cells. Intravenous injection of enzymatically inactive ATX attenuated the homing of T cells to lymphoid tissues, probably through competition with endogenous ATX and exertion of a dominant negative effect. Our results support the idea of a new and general step in the homing cascade in which the ectoenzyme ATX facilitates the entry of lymphocytes into lymphoid organs.
authors.affiliation: Department of Anatomy, Program in Immunology, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Kanda
authors.forename: Rebecca
authors.initials: R
authors.lastname: Newton
authors.forename: Russell
authors.initials: R
authors.lastname: Klein
authors.forename: Yuka
authors.initials: Y
authors.lastname: Morita
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gunn
authors.forename: Steven D
authors.initials: SD
authors.lastname: Rosen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000502:physiology*; D043264:Phosphodiesterase I / Q000502:physiology*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000502:physiology*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D000099189:Lysophospholipase D
chemical_list: D008246:Lysophospholipids; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid