title: Involvement of the lysophosphatidic acid-generating enzyme autotaxin in lymphocyte-endothelial cell interactions.
abstract: Autotaxin (ATX) is a secreted protein with lysophospholipase D activity that generates lysophosphatidic acid (LPA) from lysophosphatidylcholine. Here we report that functional ATX is selectively expressed in high endothelial venules (HEVs) of both lymph nodes and Peyer's patches. ATX expression was developmentally regulated and coincided with lymphocyte recruitment to the lymph nodes. In adults, ATX expression was independent of HEV-expressed chemokines such as CCL21 and CXCL13, innate immunity signals including those via TLR4 or MyD88, and of the extent of lymphocyte trafficking across the HEVs. ATX expression was induced in venules at sites of chronic inflammation. Receptors for the ATX enzyme product LPA were constitutively expressed in HEV endothelial cells (ECs). In vitro, LPA induced strong morphological changes in HEV ECs. Forced ATX expression caused cultured ECs to respond to lysophosphatidylcholine, up-regulating lymphocyte binding to the ECs in a LPA receptor-dependent manner under both static and flow conditions. Although in vivo depletion of circulating ATX did not affect lymphocyte trafficking into the lymph nodes, we surmise, based on the above data, that ATX expressed by HEVs acts on HEVs in situ to facilitate lymphocyte binding to ECs and that ATX in the general circulation does not play a major role in this process. Tissue-specific inactivation of ATX will verify this hypothesis in future studies of its mechanism of action.
authors.affiliation: Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
authors.forename: Tae
authors.initials: T
authors.lastname: Nakasaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Shinichi
authors.initials: S
authors.lastname: Okudaira
authors.forename: Michi
authors.initials: M
authors.lastname: Hirosawa
authors.forename: Eiji
authors.initials: E
authors.lastname: Umemoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Otani
authors.forename: Soojung
authors.initials: S
authors.lastname: Jin
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Bai
authors.forename: Haruko
authors.initials: H
authors.lastname: Hayasaka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukui
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Aozasa
authors.forename: Naoya
authors.initials: N
authors.lastname: Fujita
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuruo
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054421:Chemokine CCL21 / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000378:metabolism; D002908:Chronic Disease; D003599:Cytoskeleton / Q000187:drug effects / Q000201:enzymology; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D007249:Inflammation / Q000201:enzymology; D008198:Lymph Nodes / Q000201:enzymology; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010581:Peyer's Patches / Q000201:enzymology; D043264:Phosphodiesterase I / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D000099189:Lysophospholipase D
chemical_list: D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D008246:Lysophospholipids; D009097:Multienzyme Complexes; D053594:Myeloid Differentiation Factor 88; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D049368:Receptors, Lysophosphatidic Acid; D000099189:Lysophospholipase D; C486386:Cxcl13 protein, mouse; C471356:DOCK2 protein, mouse; C032881:lysophosphatidic acid