title: CD73-generated adenosine restricts lymphocyte migration into draining lymph nodes.
abstract: After an inflammatory stimulus, lymphocyte migration into draining lymph nodes increases dramatically to facilitate the encounter of naive T cells with Ag-loaded dendritic cells. In this study, we show that CD73 (ecto-5'-nucleotidase) plays an important role in regulating this process. CD73 produces adenosine from AMP and is expressed on high endothelial venules (HEV) and subsets of lymphocytes. Cd73(-/-) mice have normal sized lymphoid organs in the steady state, but approximately 1.5-fold larger draining lymph nodes and 2.5-fold increased rates of L-selectin-dependent lymphocyte migration from the blood through HEV compared with wild-type mice 24 h after LPS administration. Migration rates of cd73(+/+) and cd73(-/-) lymphocytes into lymph nodes of wild-type mice are equal, suggesting that it is CD73 on HEV that regulates lymphocyte migration into draining lymph nodes. The A(2B) receptor is a likely target of CD73-generated adenosine, because it is the only adenosine receptor expressed on the HEV-like cell line KOP2.16 and it is up-regulated by TNF-alpha. Furthermore, increased lymphocyte migration into draining lymph nodes of cd73(-/-) mice is largely normalized by pretreatment with the selective A(2B) receptor agonist BAY 60-6583. Adenosine receptor signaling to restrict lymphocyte migration across HEV may be an important mechanism to control the magnitude of an inflammatory response.
authors.affiliation: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City, OK 73104, USA.
authors.forename: Masahide
authors.initials: M
authors.lastname: Takedachi
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Qu
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Ebisuno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oohara
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Joachims
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: McGee
authors.forename: Emiko
authors.initials: E
authors.lastname: Maeda
authors.forename: Rodger P
authors.initials: RP
authors.lastname: McEver
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
authors.forename: Shinya
authors.initials: S
authors.lastname: Murakami
authors.forename: Thomas
authors.initials: T
authors.lastname: Krahn
authors.forename: Michael R
authors.initials: MR
authors.lastname: Blackburn
authors.forename: Linda F
authors.initials: LF
authors.lastname: Thompson
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000241:Adenosine / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D058908:Adenosine A2 Receptor Agonists; D000249:Adenosine Monophosphate / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology; D004730:Endothelium, Vascular / Q000201:enzymology / Q000276:immunology*; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D043704:Receptor, Adenosine A2B / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D014699:Venules / Q000201:enzymology / Q000276:immunology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D000631:Aminopyridines; C518875:BAY 60-6583; D008070:Lipopolysaccharides; D043704:Receptor, Adenosine A2B; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D000249:Adenosine Monophosphate; D015720:5'-Nucleotidase; D000241:Adenosine