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Published on: August 16, 2013
Neutrophil-derived Oxidants and Proteinases as Immunomodulatory Mediators in Inflammation
V Witko-Sarsat1, B Descamps-Latscha
1INSERM U25 Hôpital Necker 161 rue de Sèvres Paris 75743 France.
Abstract:
Neutrophils generate potent microbicidal molecules via the oxygen-dependent pathway, leading to the generation of reactive oxygen intermediates (ROI), and via the non-oxygen dependent pathway, consisting in the release of serine proteinases and metalloproteinases stored in granules. Over the past years, the concept has emerged that both ROI and proteinases can be viewed as mediators able to modulate neutrophil responses as well as the whole inflammatory process. This is well illustrated by the oxidative regulation of proteinase activity showing that oxidants and proteinases acts is concert to optimize the microbicidal activity and to damage host tissues. ROI and proteinases can modify the activity of several proteins involved in the control of inflammatory process. 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 endothelial cells, which is a critical step in the inflammatory process.
Insights
Reactive oxygen intermediates (ROI) and proteinases modulate neutrophil responses and inflammation. These molecules work together to enhance microbicidal activity and influence inflammatory processes like cytokine activity and neutrophil adhesion.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Neutrophils employ oxygen-dependent (reactive oxygen intermediates, ROI) and oxygen-independent (serine proteinases, metalloproteinases) pathways for microbicidal activity.
- Emerging evidence suggests ROI and proteinases act as key mediators modulating neutrophil functions and the broader inflammatory response.
Purpose of the Study:
- To explore the dual role of ROI and proteinases in regulating neutrophil responses.
- To investigate the interplay between oxidants and proteinases in controlling inflammatory processes.
- To elucidate how ROI and proteinases influence key inflammatory mediators and cellular adhesion.
Main Methods:
- Analysis of neutrophil microbicidal pathways (oxygen-dependent and independent).
- Investigation of oxidative regulation of proteinase activity.
- Examination of the effects of ROI and proteinases on inflammatory mediators (e.g., TNF-alpha, IL-8) and neutrophil adhesion.
Main Results:
- Oxidants and proteinases function in concert to optimize microbicidal activity and potentially cause host tissue damage.
- ROI and proteinases modify the activity of proteins controlling inflammation, including tumor necrosis factor-alpha and interleukin-8.
- ROI and proteinases significantly impact neutrophil adhesion to endothelial cells, a crucial inflammatory step.
Conclusions:
- Neutrophil-derived ROI and proteinases are critical regulators of inflammatory processes.
- The interaction between ROI and proteinases fine-tunes microbicidal efficacy and inflammatory cell behavior.
- Understanding these pathways offers insights into controlling inflammation and neutrophil-mediated tissue responses.
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