CD73-generated adenosine restricts lymphocyte migration into draining lymph nodes
| Autor: | Shinya Murakami, Michelle L. Joachims, Stephanie T. McGee, Yukihiko Ebisuno, Michael R. Blackburn, Hiroyuki Oohara, Dongfeng Qu, Masayuki Miyasaka, Toshiyuki Tanaka, Emiko Maeda, Thomas Krahn, Linda F. Thompson, Rodger P. McEver, Masahide Takedachi |
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| Předmět: |
Adenosine monophosphate
Lipopolysaccharides Adenosine Endothelium Adenosine A2 Receptor Agonists Lymphocyte T-Lymphocytes Immunology High endothelial venules Aminopyridines Biology Receptor Adenosine A2B Article chemistry.chemical_compound Mice Venules Cell Movement medicine Immunology and Allergy Animals L-Selectin 5'-Nucleotidase Inflammation Mice Knockout Tumor Necrosis Factor-alpha Dendritic Cells Adenosine receptor Molecular biology Adenosine Monophosphate Up-Regulation Lymphatic system medicine.anatomical_structure chemistry Lymph Endothelium Vascular Lymph Nodes medicine.drug |
| Zdroj: | Scopus-Elsevier |
| Popis: | 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 ∼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 A2B 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-α. Furthermore, increased lymphocyte migration into draining lymph nodes of cd73−/− mice is largely normalized by pretreatment with the selective A2B 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. |
| Databáze: | OpenAIRE |
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