| First Author | Conus S | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 3 | Pages | 685-98 |
| PubMed ID | 18299403 | Mgi Jnum | J:133082 |
| Mgi Id | MGI:3777708 | Doi | 10.1084/jem.20072152 |
| Citation | Conus S, et al. (2008) Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation. J Exp Med 205(3):685-98 |
| abstractText | In the resolution of inflammatory responses, neutrophils rapidly undergo apoptosis. We describe a new proapoptotic pathway in which cathepsin D directly activates caspase-8. Cathepsin D is released from azurophilic granules in neutrophils in a caspase-independent but reactive oxygen species-dependent manner. Under inflammatory conditions, the translocation of cathepsin D in the cytosol is blocked. Pharmacological or genetic inhibition of cathepsin D resulted in delayed caspase activation and reduced neutrophil apoptosis. Cathepsin D deficiency or lack of its translocation in the cytosol prolongs innate immune responses in experimental bacterial infection and in septic shock. Thus, we identified a new function of azurophilic granules that is in addition to their role in bacterial defense mechanisms: to regulate the life span of neutrophils and, therefore, the duration of innate immune responses through the release of cathepsin D. |
