Glycosaminoglycan degradation by selected reactive oxygen species.

SIGNIFICANCE: Inflammatory diseases (such as arthritis) of the extracellular matrix (ECM) are of considerable socioeconomic significance. There is clear evidence that reactive oxygen species (ROS) and nitrogen species released by, for instance, neutrophils contribute to the degradation of the ECM. Here we will focus on the ROS-induced degradation of the glycosaminoglycans, one important component of the ECM. RECENT ADVANCES: The recently developed "anti-TNF-α" therapy is primarily directed against neutrophilic granulocytes that are powerful sources of ROS. Therefore, a more detailed look into the mechanisms of the reactions of these ROS is reasonable. CRITICAL ISSUES: Since both enzymes and ROS contribute to the pathogenesis of inflammatory diseases, it is very difficult to estimate the contributions of the individual species in a complex biological environment. This particularly applies as many products are not stable but only transient products that decompose in a time-dependent manner. Thus, the development of suitable analytical methods as well as the establishment of useful biomarkers is a challenging aspect. FUTURE DIRECTIONS: If the mechanisms of ECM destruction are understood in more detail, then the development of suitable drugs to treat inflammatory diseases will be hopefully much more successful.