Cell-derived Oxidants and Their Effects on HA

Neutrophil-mediated HA degradation was shown to be increased in the presence of the MPO inhibitor azide [104] and is inhibited by dimethylsulf-oxide [105] but not by metal chelators such as deferoxamine (DFO) or diethy-lenetriamine pentaacetic acid (DTPA). Selected specific enzymes are able to prevent the degradation of HA by stimulated neutrophils [106]. Interestingly, the ability to degrade HA seems to be specific to PMA-stimulated PMNs and is not observed with neutrophils stimulated by other compounds such as formyl-methionyl-leucyl-phenylalanine, concanavalin-A or digitonin. This may be related to the increased concentrations of H O generated in response to these stimuli, or a greater release of specific enzymes that consume the relevant reactive species [107]. 

In addition to neutrophils, endothelial cells were also used to degrade a variety of important GAGs. Although these cells were able to degrade heparin, that is very sensitive to a NO-dependent deaminative cleavage, HA is not susceptible to this pathway and thus, it can be concluded that endothelial cells are not capable of generating ROS that lead to the degradation of HA [91]. 

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