Leopold Jenny, Schiller Jürgen
Institute for Medical Physics and Biophysics, Medical Faculty, Leipzig University, 04103 Leipzig, Germany.
Antioxidants (Basel). 2024 Jul 29;13(8):921. doi: 10.3390/antiox13080921.
Chronic rheumatic diseases such as rheumatoid arthritis (RA) are characterized by a dysregulated immune response and persistent inflammation. The large number of neutrophilic granulocytes in the synovial fluid (SF) from RA patients leads to elevated enzyme activities, for example, from myeloperoxidase (MPO) and elastase. Hypochlorous acid (HOCl), as the most important MPO-derived product, is a strong reactive oxygen species (ROS) and known to be involved in the processes of cartilage destruction (particularly regarding the glycosaminoglycans). This review will discuss open questions about the contribution of HOCl in RA in order to improve the understanding of oxidative tissue damaging. First, the (chemical) composition of articular cartilage and SF and the mechanisms of cartilage degradation will be discussed. Afterwards, the products released by neutrophils during inflammation will be summarized and their effects towards the individual, most abundant cartilage compounds (collagen, proteoglycans) and selected cellular components (lipids, DNA) discussed. New developments about neutrophil extracellular traps (NETs) and the use of antioxidants as drugs will be outlined, too. Finally, we will try to estimate the effects induced by these different agents and their contributions in RA.
类风湿关节炎(RA)等慢性风湿性疾病的特征是免疫反应失调和持续炎症。类风湿关节炎患者滑液(SF)中大量的中性粒细胞会导致酶活性升高,例如髓过氧化物酶(MPO)和弹性蛋白酶的活性升高。次氯酸(HOCl)作为MPO产生的最重要产物,是一种强活性氧(ROS),已知参与软骨破坏过程(特别是关于糖胺聚糖)。本综述将讨论关于HOCl在类风湿关节炎中的作用的一些未解决问题,以增进对氧化组织损伤的理解。首先,将讨论关节软骨和滑液的(化学)组成以及软骨降解的机制。之后,将总结炎症期间中性粒细胞释放的产物,并讨论它们对单个最丰富的软骨成分(胶原蛋白、蛋白聚糖)和选定细胞成分(脂质、DNA)的影响。还将概述中性粒细胞胞外陷阱(NETs)的新进展以及抗氧化剂作为药物的应用。最后,我们将尝试评估这些不同因素诱导的效应及其在类风湿关节炎中的作用。