Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis

Escherichia (E.) coli is the most common causative pathogen in peritonitis, the second most common cause of sepsis. Granzymes (gzms) are serine proteases traditionally implicated in cytotoxicity and, more recently, in the inflammatory response. We here sought to investigate the role of gzms in the h...

Full description

Saved in:

Bibliographic Details
Published in:	Mediators of inflammation 2017-01, Vol.2017, p.4137563-11
Main Authors:	García-Laorden, M. Isabel, Stroo, Ingrid, Terpstra, Sanne, Florquin, Sandrine, Medema, Jan Paul, van´t Veer, Cornelis, de Vos, Alex F., van der Poll, Tom
Format:	Article
Language:	eng
Subjects:	Abdomen Analysis Animals Apoptosis Bacterial infections Causes of Cytokines Cytotoxicity E coli Escherichia coli Escherichia coli - pathogenicity Experiments Female Gangrene Gram-positive bacteria Granzymes - genetics Granzymes - metabolism Health aspects Infections Laboratories Liver Lungs Male Medical research Mice Mice, Inbred C57BL Neutrophil Infiltration - genetics Neutrophil Infiltration - physiology Nucleosomes - metabolism Peritonitis Peritonitis - genetics Peritonitis - metabolism Proteases Rodents Sepsis Sepsis - genetics Sepsis - metabolism Studies
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Escherichia (E.) coli is the most common causative pathogen in peritonitis, the second most common cause of sepsis. Granzymes (gzms) are serine proteases traditionally implicated in cytotoxicity and, more recently, in the inflammatory response. We here sought to investigate the role of gzms in the host response to E. coli-induced peritonitis and sepsis in vivo. For this purpose, we used a murine model of E. coli intraperitoneal infection, resembling the clinical condition commonly associated with septic peritonitis by this bacterium, in wild-type and gzmA-deficient (gzmA−/−), gzmB−/−, and gzmAxB−/−mice. GzmA and gzmB were predominantly expressed by natural killer cells, and during abdominal sepsis, the percentage of these cells expressing gzms in peritoneal lavage fluid decreased, while the amount of expression in the gzm+ cells increased. Deficiency of gzmA and/or gzmB was associated with increased bacterial loads, especially in the case of gzmB at the primary site of infection at late stage sepsis. While gzm deficiency did not impact neutrophil recruitment into the abdominal cavity, it was accompanied by enhanced nucleosome release at the primary site of infection, earlier hepatic necrosis, and more renal dysfunction. These results suggest that gzms influence bacterial growth and the host inflammatory response during abdominal sepsis caused by E. coli.
ISSN:	0962-9351 1466-1861