NEUTROPHIL-DERIVED OXIDANTS AND PROTEINASES AS IMMUNOMODULATORY MEDIATORS IN INFLAMMATION

NEUTROPHILS generate potent microbicidal molecules via the oxygen-depe ndent pathway, leading to the generation of reactive oxygen intermedia tes (ROI), and via the non-oxygen dependent pathway, consisting in the release of serine proteinases and metalloproteinases stored in granul es. Over the past years, the concept has emerged that both ROI and pro teinases can be viewed as mediators able to modulate neutrophil respon ses as well as the whole inflammatory process. This is well illustrate d by the oxidative regulation of proteinase activity showing that oxid ants and proteinases acts is concert to optimize the microbicidal acti vity and to damage host tissues. ROI and proteinases can modify the ac tivity of several proteins involved in the control of inflammatory pro cess. Among them, tumour necrosis factor-alpha and interleukin-8, are elective targets for such a modulation. Moreover, ROI and proteinases are also able to modulate the adhesion process of neutrophils to endot helial cells, which is a critical step in the inflammatory process.