[Frontiers in Bioscience 14, 3409-3418, January 1, 2009]

Neutrophil-derived serine proteases modulate innate immune responses

Ulf Meyer-Hoffert1

1Department of Dermatology, University Schleswig-Holstein, Kiel, Germany

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Conversion of cytokines and growth factors
3.1. Proteinase 3 converts TNF-alpha
3.2. Conversion of IL-1 by proteinase 3
3.3. Proteinase 3 activates IL-18
4. Activation of receptors
4.1. Activation of PARs
4.2. HLE activates TLR4
4.3. HLE activates EGFR
4.4. Cathepsin G activates the formyl peptide receptor
5. Caspase-like Activity
6. Integrin Clustering
7. Proteolytic modifaction of receptors and cytokines
8. Perspective
9. Acknowledgement
10. References

1. ABSTRACT

The serine proteases cathepsin G, human leukocyte elastase and proteinase 3 are major contents of neutrophils and are released at sites of inflammation. Although the traditional function of neutrophil-derived antimicrobial proteases is to ingest and kill bacteria, recent studies provided evidence that these proteases are able to activate specifically pro-inflammatory cytokines and lead to the activation of different receptors. Neutrophil serine proteases might therefore be important regulators of the inflammatory innate immune response and are interesting targets for new therapeutic approaches against inflammatory disorders. This review summarizes the current knowledge on the molecular regulation of the innate immune response by neutrophil-derived serine proteases.