Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs.
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.
Kanda
Hidenobu
H
Department of Anatomy, Program in Immunology, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143, USA.
Newton
Rebecca
R
Klein
Russell
R
Morita
Yuka
Y
Gunn
Michael D
MD
Rosen
Steven D
SD
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
D008246:Lysophospholipids; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid