Research output: Contribution to journal › Article › Academic › peer-review
Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis. / García-Laorden, M. Isabel; Stroo, Ingrid; Terpstra, Sanne et al.
In: Mediators of inflammation, Vol. 2017, 2017, p. 4137563.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis
AU - García-Laorden, M. Isabel
AU - Stroo, Ingrid
AU - Terpstra, Sanne
AU - Florquin, Sandrine
AU - Medema, Jan Paul
AU - van T Veer, Cornelis
AU - de Vos, Alex F.
AU - van der Poll, Tom
PY - 2017
Y1 - 2017
N2 - 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
AB - 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
U2 - 10.1155/2017/4137563
DO - 10.1155/2017/4137563
M3 - Article
C2 - 28694562
VL - 2017
SP - 4137563
JO - Mediators of inflammation
JF - Mediators of inflammation
SN - 0962-9351
ER -
ID: 3892662