Roberts Veena, Stagg John, Dwyer Karen M
Immunology Research Centre, St. Vincent's Hospital Melbourne and Department of Medicine, The University of Melbourne , Melbourne, VIC , Australia.
Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Faculté de Pharmacie et Institut du Cancer de Montréal , Montréal, QC , Canada.
Front Immunol. 2014 Feb 18;5:64. doi: 10.3389/fimmu.2014.00064. eCollection 2014.
Extracellular adenosine is a potent immunomodulatory molecule that accumulates in states of inflammation. Nucleotides such as adenosine triphosphate and adenosine diphosphate are release from injured and necrotic cells and hydrolyzed to adenosine monophosphate and adenosine by the concerted action of the ectonucleotidases CD39 and CD73. Accumulating evidence suggest that purinergic signaling is involved in the inflammatory response that accompanies acute rejection and chronic allograft dysfunction. Modification of the purinergic pathway has been shown to alter graft survival in a number of solid organ transplant models and the response to ischemia-reperfusion injury (IRI). Furthermore, the purinergic pathway is intrinsically involved in B and T cell biology and function. Although T cells have traditionally been considered the orchestrators of acute allograft rejection, a role for B cells in chronic allograft loss is being increasingly appreciated. This review focuses on the role of the ectonucleotidases CD39 and CD73 and adenosine signaling in solid organ transplantation including the effects on IRI and T and B cell biology.
细胞外腺苷是一种有效的免疫调节分子，在炎症状态下会蓄积。三磷酸腺苷和二磷酸腺苷等核苷酸从受损和坏死细胞中释放出来，并通过外核苷酸酶CD39和CD73的协同作用水解为单磷酸腺苷和腺苷。越来越多的证据表明，嘌呤能信号传导参与了伴随急性排斥反应和慢性移植物功能障碍的炎症反应。在许多实体器官移植模型中，嘌呤能途径的改变已被证明会改变移植物的存活以及对缺血再灌注损伤（IRI）的反应。此外，嘌呤能途径在B细胞和T细胞的生物学特性及功能中起着内在作用。虽然传统上认为T细胞是急性移植物排斥反应的主导者，但B细胞在慢性移植物丢失中的作用正越来越受到重视。本综述重点关注外核苷酸酶CD39和CD73以及腺苷信号传导在实体器官移植中的作用，包括对IRI以及T细胞和B细胞生物学的影响。
