Department of Anesthesiology, Kansai Medical University , Osaka , Japan.
Immunopharmacol Immunotoxicol. 2013 Oct;35(5):558-66. doi: 10.3109/08923973.2013.822509. Epub 2013 Aug 8.
Dexmedetomidine is a highly-selective α2-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.
右美托咪定是一种高选择性的α2-肾上腺素能受体激动剂，用于重症监护病房中危重病患者的镇静。外周组织中的树突状细胞（DCs）感知某些外来抗原并摄取和处理它们，同时迁移到区域性淋巴结。然后，DCs 将处理过的抗原呈现在表面，以刺激认知淋巴细胞的克隆增殖，从而建立适应性免疫。在鼠骨髓来源的 DCs 中，右美托咪定显著延迟卵清蛋白的细胞内蛋白水解降解，而不影响吞噬作用，降低表面分子 I-A(b)和 CD86 的表达，并抑制认知辅助 T 细胞增殖。此外，右美托咪定在体外使用 Matrigel 迁移测定法和体内使用足垫-腘淋巴结迁移测定法均显著抑制 DC 迁移，这可能归因于抑制 IV 型胶原酶/明胶酶活性。最后，用右美托咪定处理的 DC 进行疫苗接种可显著抑制体内接触超敏反应。这些结果表明，右美托咪定可能通过抑制 DC 抗原加工/呈递和迁移来抑制免疫。
