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...
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2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/4137563 |
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| author | M. Isabel García-Laorden Ingrid Stroo Sanne Terpstra Sandrine Florquin Jan Paul Medema Cornelis van´t Veer Alex F. de Vos Tom van der Poll |
| author_facet | M. Isabel García-Laorden Ingrid Stroo Sanne Terpstra Sandrine Florquin Jan Paul Medema Cornelis van´t Veer Alex F. de Vos Tom van der Poll |
| author_sort | M. Isabel García-Laorden |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1e7e729e1a2a405c85613d9fd76caa1d |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1e7e729e1a2a405c85613d9fd76caa1d2025-02-03T01:20:15ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/41375634137563Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and SepsisM. Isabel García-Laorden0Ingrid Stroo1Sanne Terpstra2Sandrine Florquin3Jan Paul Medema4Cornelis van´t Veer5Alex F. de Vos6Tom van der Poll7Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, NetherlandsDepartment of Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, NetherlandsEscherichia (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.http://dx.doi.org/10.1155/2017/4137563 |
| spellingShingle | M. Isabel García-Laorden Ingrid Stroo Sanne Terpstra Sandrine Florquin Jan Paul Medema Cornelis van´t Veer Alex F. de Vos Tom van der Poll Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis Mediators of Inflammation |
| title | Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis |
| title_full | Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis |
| title_fullStr | Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis |
| title_full_unstemmed | Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis |
| title_short | Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis |
| title_sort | expression and function of granzymes a and b in escherichia coli peritonitis and sepsis |
| url | http://dx.doi.org/10.1155/2017/4137563 |
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