Table 1.
Effects of neutrophil serine proteases on selected biological targets
| Targets | Proteases | Potential biological effects |
|---|---|---|
| Chemokines | ||
| CCL3 | CG, NE, PR3 | Abrogation of chemotactic activity |
| CCL5 | CG | N-terminal truncation and ↓ chemotactic activity |
| CCL15 | CG | N-terminal truncation and ↑ chemotactic activity |
| CCL23 | CG, NE | N- and C-terminal truncation and ↑ affinity to receptors |
| CXCL2 | CG | ↑ release from neutrophils |
| CXCL5 | CG | N-terminal truncation and ↑ chemotactic activity |
| CXCL7 | CG | Conversion of CTAP-III to CXCL7 |
| CXCL8 | PR3 | N-terminal truncation and ↑ chemotactic activity |
| CXCL12 | CG, NE | Abrogation of chemotactic activity |
| Chemerin | CG, NE | Conversion of prochemerin to chemerin |
| Cytokines | ||
| IL-1β | PR3 | Conversion of pro-IL-1β to soluble, active IL-1β |
| IL-6 | CG, NE, PR3 | Degradation and inactivation |
| IL-18 | PR3, NE | Conversion of pro-IL-18 to mature IL-8 by PR3; proteolysis and abrogation of activity by NE |
| IL-32 | PR3 | Increase in activity |
| TNF-α | PR3, CG, NE | Activation of membrane-bound pro-TNF-α by CG, NE, and PR3; degradation by CG and NE |
| Growth factors | ||
| TGF-β | NE | Release of membrane-bound TGF-β to activate EGFR; cleavage of LTBP to release latent TGF-β |
| Antimicrobial peptides | ||
| LL-37 | PR3 | Conversion of hCAP18 to LL-37 |
| Receptors | ||
| αIIβ3 integrin | NE | ↑ platelet aggregation |
| CD14 | CG, NE | ↓ LPS-induced cell activation; ↓ ability of macrophages to recognize apoptotic cells |
| CD43 | NE | ↑ cell spreading |
| CD87 | CG, NE | ↓ urokinase binding; generation of chemotactic fragments |
| CR1 | NE | Release of sCR1 and inhibition of complement activation |
| CXCR4 | NE | N-terminal proteolysis, ↓ CXCL12 binding |
| FPR | CG | Induction of PKCζ translocation, Ca+ flux, and chemotaxis |
| IL-6R | CG | Inactivation |
| PAR1 | CG, NE, PR3 | Inactivation |
| PAR2 | CG, NE, PR3 | Activation and inactivation of the receptor through distinct cleavage sites |
| PAR4 | CG | Activation |
| TLR4 | NE | Activation through a MyD88/IRAK/TRAF-6-dependent pathway |
| TNFR | NE | Inactivation of the p75 receptor |
| Adhesion molecules | ||
| E-cadherins | CG, NE | ↑ neutrophil transmigration |
| ICAM-1 | CG, NE | ↑ neutrophil infiltration |
| VCAM-1 | CG, NE | ↑ mobilization of hematopoietic cells |
| Apoptotic molecules | ||
| NF-κB | NE, PR3 | Induction of apoptosis |
| p21 | PR3 | Induction of apoptosis |