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Detecting Migration and Infiltration of Neutrophils in Mice
Published on: February 6, 2020
Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute
April M Adkison1, Sofia Z Raptis, Diane G Kelley
1Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
The Journal of Clinical Investigation
|February 6, 2002
Summary
Dipeptidyl peptidase I (DPPI) deficiency protects against arthritis by inactivating neutrophil proteases. This study reveals DPPI
Area of Science:
- Immunology
- Inflammation Biology
- Protease Function
Background:
- Leukocyte recruitment is vital for host defense but excessive inflammation causes tissue damage.
- Neutrophil-derived serine proteases (cathepsin G, neutrophil elastase, proteinase 3) are key inflammatory mediators.
- The role of these proteases and their activator, dipeptidyl peptidase I (DPPI), in inflammation requires further investigation.
Purpose of the Study:
- To investigate the role of DPPI and neutrophil-derived serine proteases in inflammatory conditions.
- To determine if DPPI is essential for the activation of these proteases.
- To assess the impact of DPPI deficiency on arthritis and other inflammatory responses.
Main Methods:
- Generation of dipeptidyl peptidase I (DPPI)-deficient mice.
- Assessment of neutrophil chemotaxis and accumulation in vivo and in vitro.
- Induction of arthritis via passive transfer of anti-type II collagen antibodies.
- Evaluation of inflammatory responses in a subcutaneous air pouch model.
- Analysis of cytokine production (TNF-alpha, IL-1 beta).
Main Results:
- DPPI is required for the full activation of neutrophil-derived serine proteases (cathepsin G, neutrophil elastase, proteinase 3).
- DPPI-deficient mice are protected against anti-collagen antibody-induced arthritis, showing no neutrophil joint accumulation.
- Mice lacking neutrophil proteases (NE(-/-) x CG(-/-)) are also resistant to arthritis.
- Protease-deficient mice exhibit reduced responses to zymosan and immune complex inflammation, with decreased local TNF-alpha and IL-1 beta production.
Conclusions:
- DPPI plays a critical role in activating neutrophil-derived serine proteases involved in inflammation.
- Neutrophil-derived serine proteases are implicated in the pathogenesis of arthritis and other inflammatory conditions.
- DPPI and these proteases regulate local cytokine production at inflammatory sites, highlighting a potential therapeutic target.
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