Characterization of the cathepsin D in Procambarus clarkii and its biological role in innate immune responses

2020 ◽  
Vol 111 ◽  
pp. 103766
Author(s):  
Xiao-Min Yu ◽  
Jia-Le Chen ◽  
Muhammad Nadeem Abbas ◽  
Isma Gul ◽  
Saima Kausar ◽  
...  
PLoS ONE ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. e0235745 ◽  
Author(s):  
Ramona Nudischer ◽  
Kasper Renggli ◽  
Andreas Hierlemann ◽  
Adrian B. Roth ◽  
Cristina Bertinetti-Lapatki

2008 ◽  
Vol 205 (3) ◽  
pp. 685-698 ◽  
Author(s):  
Sébastien Conus ◽  
Remo Perozzo ◽  
Thomas Reinheckel ◽  
Christoph Peters ◽  
Leonardo Scapozza ◽  
...  

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.


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