Barker Catriona E, Ali Simi, O'Boyle Graeme, Kirby John A
Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Immunology. 2014 Oct;143(2):138-45. doi: 10.1111/imm.12332.
Oxidative stress is a major and recurring cause of damage during inflammation, especially following organ transplantation. Initial ischaemia-reperfusion injury causes the production of many reactive oxygen and nitrogen species, and subsequent recruitment and activation of inflammatory cells can lead to further oxidative stress. This stress is well known to cause damage at the cellular level, for example by induction of senescence leading to the production of a characteristic senescence-associated secretory phenotype. Chemokines are an important component of the senescence-associated secretory phenotype, recruiting further leucocytes and reinforcing the stress and senescence responses. As well as inducing the production of proteins, including chemokines, oxidative stress can alter proteins themselves, both directly and by induction of enzymes capable of modification. These alterations can lead to important modifications to their biological activity and also alter detection by some antibodies, potentially limiting the biological relevance of some immunochemical and proteomic biomarkers. Peroxynitrite, a reactive nitrogen species generated during inflammation and ischaemia, can cause such modifications by nitrating chemokines. Matrix metalloproteinases, released by many stressed cells, can cleave chemokines, altering function, while peptidylarginine deiminases can inactivate certain chemokines by citrullination. This review discusses the relationship between inflammation and post-translational modification, focusing on the functional modulation of transplant-relevant pro-inflammatory chemokines.
氧化应激是炎症过程中造成损伤的主要且反复出现的原因，在器官移植后尤为如此。最初的缺血再灌注损伤会导致产生许多活性氧和氮物质，随后炎症细胞的募集和激活会导致进一步的氧化应激。众所周知，这种应激会在细胞水平上造成损伤，例如通过诱导衰老导致产生特征性的衰老相关分泌表型。趋化因子是衰老相关分泌表型的重要组成部分，会募集更多白细胞并增强应激和衰老反应。除了诱导包括趋化因子在内的蛋白质产生外，氧化应激还可直接或通过诱导能够进行修饰的酶来改变蛋白质本身。这些改变会导致其生物学活性发生重要修饰，还会改变某些抗体的检测结果，可能会限制一些免疫化学和蛋白质组学生物标志物的生物学相关性。过氧亚硝酸盐是炎症和缺血过程中产生的一种活性氮物质，可通过使趋化因子硝化而导致此类修饰。许多应激细胞释放的基质金属蛋白酶可切割趋化因子，改变其功能，而肽基精氨酸脱氨酶可通过瓜氨酸化使某些趋化因子失活。本综述讨论了炎症与翻译后修饰之间的关系，重点关注与移植相关的促炎趋化因子的功能调节。
