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Proteases produced by activated neutrophils are able to release soluble CD23 fragments endowed with proinflammatory
1INSERM U343, Hôpital de L'Archet, F-06202 Nice cedex 3, France.
Abstract:
Polymorphonuclear neutrophils (PMNs) are the major source of proteolytic activities involved mainly in tissue injuries observed in chronic inflammatory disorders. High levels of soluble forms of CD23 (the low-affinity receptor for IgE) were found in biological fluids from these patients, and recent reports focused on a CD23-mediated regulation of inflammatory response. In this context, we show here that co-culture of activated PMN with CD23+ B cells resulted in a drastic release of soluble CD23 fragments from the cell surface. This cleavage was inhibited by serine proteases inhibitors, including a1-antitrypsin. We next demonstrated that purified human leukocyte elastase or cathepsin G efficiently cleaved membrane CD23 on B cells with a high specificity. Soluble fragments released by serine proteases-mediated CD23 proteolysis stimulated resting monocytes to produce oxidative burst and proinflammatory cytokine without any co-stimulatory signal. This work strongly supports the idea that the capacity of PMN-derived proteases to release soluble forms of CD23 participates in the inflammatory process mediated by these cells.
Insights
Activated neutrophils release soluble CD23 fragments, which promote inflammation. Serine proteases from neutrophils cleave CD23 on B cells, stimulating monocytes and contributing to inflammatory disorders.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Polymorphonuclear neutrophils (PMNs) are key players in tissue damage during chronic inflammation.
- Elevated soluble CD23 levels are observed in patients with inflammatory conditions.
- CD23 is implicated in regulating inflammatory responses.
Purpose of the Study:
- To investigate the mechanism of soluble CD23 fragment release.
- To determine the role of PMN-derived proteases in CD23 cleavage.
- To assess the inflammatory potential of CD23 fragments generated by proteolysis.
Main Methods:
- Co-culture of activated PMNs with CD23+ B cells.
- Treatment with serine protease inhibitors and purified proteases (leukocyte elastase, cathepsin G).
- Stimulation assays with monocytes using released CD23 fragments.
Main Results:
- Activated PMNs induced significant release of soluble CD23 from B cells.
- Serine proteases, notably leukocyte elastase and cathepsin G, were identified as key enzymes cleaving membrane CD23.
- Inhibitors of serine proteases, like a1-antitrypsin, blocked CD23 cleavage.
- Soluble CD23 fragments stimulated monocytes to produce oxidative burst and pro-inflammatory cytokines.
Conclusions:
- PMN-derived serine proteases cleave CD23 on B cells, releasing soluble fragments.
- These soluble CD23 fragments possess pro-inflammatory activity, stimulating monocytes.
- This mechanism contributes to the inflammatory processes in chronic inflammatory disorders.