PMID- 23927488 OWN - NLM STAT- MEDLINE DCOM- 20140415 LR - 20130923 IS - 1532-2513 (Electronic) IS - 0892-3973 (Linking) VI - 35 IP - 5 DP - 2013 Oct TI - Suppression of phagosome proteolysis and Matrigel migration with the alpha2-adrenergic receptor agonist dexmedetomidine in murine dendritic cells. PG - 558-66 LID - 10.3109/08923973.2013.822509 [doi] AB - Dexmedetomidine is a highly-selective alpha2-adrenergic receptor agonist used for sedation of critically ill patients in an intensive care setting. Dendritic cells (DCs) in peripheral tissues sense certain foreign antigens and ingest and process them, while migrating to the regional lymph node. Then, DCs present the processed antigen on their surface to stimulate the clonal proliferation of cognitive lymphocytes, leading to the establishment of adaptive immunity. In murine bone marrow-derived DCs, dexmedetomidine significantly delayed the intracellular proteolytic degradation of ovalbumin, while it did not affect phagocytosis, decreased the expression of the surface molecules I-A(b) and CD86, and suppressed cognitive helper T-cell proliferation. Furthermore, dexmedetomidine significantly suppressed DC migration both in vitro, using a Matrigel migration assay, and in vivo, using a foot pad-popliteal lymph node migration assay, which may be ascribed to the inhibition of type IV collagenase/gelatinase activity. Finally, vaccination with dexmedetomidine-treated DCs significantly suppressed the contact hypersensitivity reaction in vivo. These results indicate that dexmedetomidine may suppress immunity by inhibiting DC antigen processing/presentation and migration. FAU - Ueshima, Hironobu AU - Ueshima H AD - Department of Anesthesiology, Kansai Medical University , Osaka , Japan. FAU - Inada, Takefumi AU - Inada T FAU - Shingu, Koh AU - Shingu K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130808 PL - England TA - Immunopharmacol Immunotoxicol JT - Immunopharmacology and immunotoxicology JID - 8800150 RN - 0 (Adrenergic alpha-2 Receptor Agonists) RN - 0 (Drug Combinations) RN - 0 (Laminin) RN - 0 (Proteoglycans) RN - 119978-18-6 (matrigel) RN - 67VB76HONO (Dexmedetomidine) RN - 9007-34-5 (Collagen) SB - IM MH - Adoptive Transfer MH - Adrenergic alpha-2 Receptor Agonists/*pharmacology MH - Animals MH - Antigen Presentation/drug effects/immunology MH - Cell Movement/*drug effects/immunology MH - Collagen/chemistry MH - Dendritic Cells/cytology/enzymology/*immunology MH - Dermatitis, Contact/enzymology/immunology/therapy MH - Dexmedetomidine/*pharmacology MH - Drug Combinations MH - Laminin/chemistry MH - Male MH - Mice MH - Phagosomes/*immunology/metabolism MH - Proteoglycans/chemistry MH - Proteolysis/*drug effects MH - Vaccination EDAT- 2013/08/10 06:00 MHDA- 2014/04/16 06:00 CRDT- 2013/08/10 06:00 PHST- 2013/08/10 06:00 [entrez] PHST- 2013/08/10 06:00 [pubmed] PHST- 2014/04/16 06:00 [medline] AID - 10.3109/08923973.2013.822509 [doi] PST - ppublish SO - Immunopharmacol Immunotoxicol. 2013 Oct;35(5):558-66. doi: 10.3109/08923973.2013.822509. Epub 2013 Aug 8.