Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States.
Department of Pediatric Surgery, McGovern Medical School, Children's Memorial Hermann Hospital, The University of Texas Health Science Center at Houston, Houston, TX, United States.
Front Immunol. 2019 Jul 16;10:1633. doi: 10.3389/fimmu.2019.01633. eCollection 2019.
Purine nucleotides and nucleosides are at the center of biologic reactions. In particular, adenosine triphosphate (ATP) is the fundamental energy currency of cellular activity and adenosine has been demonstrated to play essential roles in human physiology and pathophysiology. In this review, we examine the role of purinergic signaling in acute and chronic pulmonary inflammation, with emphasis on ATP and adenosine. ATP is released into extracellular space in response to cellular injury and necrosis. It is then metabolized to adenosine monophosphate (AMP) via ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and further hydrolyzed to adenosine via ecto-5'-nucleotidase (CD73). Adenosine signals via one of four adenosine receptors to exert pro- or anti-inflammatory effects. Adenosine signaling is terminated by intracellular transport by concentrative or equilibrative nucleoside transporters (CNTs and ENTs), deamination to inosine by adenosine deaminase (ADA), or phosphorylation back into AMP via adenosine kinase (AK). Pulmonary inflammatory and hypoxic conditions lead to increased extracellular ATP, adenosine diphosphate (ADP) and adenosine levels, which translates to increased adenosine signaling. Adenosine signaling is central to the pulmonary injury response, leading to various effects on inflammation, repair and remodeling processes that are either tissue-protective or tissue destructive. In the acute setting, particularly through activation of adenosine 2A and 2B receptors, adenosine signaling serves an anti-inflammatory, tissue-protective role. However, excessive adenosine signaling in the chronic setting promotes pro-inflammatory, tissue destructive effects in chronic pulmonary inflammation.
嘌呤核苷酸和核苷处于生物反应的中心。特别是三磷酸腺苷（ATP）是细胞活动的基本能量货币，腺苷已被证明在人类生理学和病理生理学中发挥重要作用。在这篇综述中，我们研究了嘌呤能信号在急性和慢性肺部炎症中的作用，重点是 ATP 和腺苷。ATP 会在细胞损伤和坏死时被释放到细胞外空间。然后，它通过外核苷酸三磷酸二磷酸水解酶-1（CD39）代谢为一磷酸腺苷（AMP），并通过外切 5'-核苷酸酶（CD73）进一步水解为腺苷。腺苷通过四种腺苷受体之一发挥促炎或抗炎作用。腺苷信号通过协同或平衡核苷转运蛋白（CNTs 和 ENTs）的细胞内转运、腺苷脱氨酶（ADA）脱氨为肌苷或腺苷激酶（AK）将其磷酸化为 AMP 来终止。肺部炎症和缺氧条件会导致细胞外 ATP、二磷酸腺苷（ADP）和腺苷水平升高，从而导致腺苷信号增加。腺苷信号是肺损伤反应的核心，导致对炎症、修复和重塑过程产生各种影响，这些影响既有组织保护作用，也有组织破坏作用。在急性情况下，特别是通过激活腺苷 2A 和 2B 受体，腺苷信号发挥抗炎、组织保护作用。然而，在慢性情况下，过多的腺苷信号会促进慢性肺部炎症中的促炎、组织破坏作用。
