OBJECTIVE: Previous studies have implicated a role of peptidoglycan in the pathophysiology of organ injury in sepsis. However, the systemic response to, and organ injury caused by, peptidoglycan have been scarcely studied in vivo. DESIGN: Prospective, randomized study. SETTING: University-based research laboratory. SUBJECTS: Fifty-seven anesthetized, male Wistar rats. INTERVENTIONS: After surgical preparation, anaesthetized rats were administered 3 mg/kg Staphylococcus aureus peptidoglycan (n = 9), 10 mg/kg S. aureus peptidoglycan (n = 14), or an equal volume of saline (sham, n = 12) in the jugular vein over a 10-min period. MEASUREMENTS AND MAIN RESULTS: Injection of low-dose peptidoglycan (3 mg/kg) had no measurable effects on the rats. In contrast, high-dose peptidoglycan (10 mg/kg) caused increased serum values of aspartate aminotransferase (p < or =.005), alanine aminotransferase (p < or =.001), gamma-glutamyltransferase, and bilirubin (p < or =.05) (indicators of liver injury/dysfunction) as well as a moderate, but significant, increase in serum creatinine and urea (p < or =.05) (indicators of renal dysfunction). Plasma analyses showed a substantial increase in plasma values of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 (p < or =.05 for all vs. sham) at 1 and 3 hrs (enzyme-linked immunosorbent assay). This was accompanied by accumulation of messenger RNAs for tumor necrosis factor-alpha, interleukin-6, and interleukin-10 in both the liver and the lung (p < or =.05 for all cytokines vs. sham) (real-time polymerase chain reaction). Peptidoglycan also caused increased DNA binding of nuclear factor-kappaB (band-shift assays) and phosphorylation of c-Jun and Jun N-terminal kinase (Western blots). In the kidney, interleukin-6 messenger RNA was increased, whereas Toll-like receptor 4 messenger RNA was significantly decreased. CONCLUSIONS: These results demonstrate that injection of peptidoglycan alone causes organ injury/dysfunction, organ inflammation, and systemic inflammation in the rat, involving nuclear factor-kappaB and possibly activator protein 1. These data support the contention that peptidoglycan is a contributing factor in the pathophysiology of organ injury in sepsis.
OBJECTIVE: Previous studies have implicated a role of peptidoglycan in the pathophysiology of organ injury in sepsis. However, the systemic response to, and organ injury caused by, peptidoglycan have been scarcely studied in vivo. DESIGN: Prospective, randomized study. SETTING: University-based research laboratory. SUBJECTS: Fifty-seven anesthetized, male Wistar rats. INTERVENTIONS: After surgical preparation, anaesthetized rats were administered 3 mg/kg Staphylococcus aureus peptidoglycan (n = 9), 10 mg/kg S. aureus peptidoglycan (n = 14), or an equal volume of saline (sham, n = 12) in the jugular vein over a 10-min period. MEASUREMENTS AND MAIN RESULTS: Injection of low-dose peptidoglycan (3 mg/kg) had no measurable effects on the rats. In contrast, high-dose peptidoglycan (10 mg/kg) caused increased serum values of aspartate aminotransferase (p < or =.005), alanine aminotransferase (p < or =.001), gamma-glutamyltransferase, and bilirubin (p < or =.05) (indicators of liver injury/dysfunction) as well as a moderate, but significant, increase in serum creatinine and urea (p < or =.05) (indicators of renal dysfunction). Plasma analyses showed a substantial increase in plasma values of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 (p < or =.05 for all vs. sham) at 1 and 3 hrs (enzyme-linked immunosorbent assay). This was accompanied by accumulation of messenger RNAs for tumor necrosis factor-alpha, interleukin-6, and interleukin-10 in both the liver and the lung (p < or =.05 for all cytokines vs. sham) (real-time polymerase chain reaction). Peptidoglycan also caused increased DNA binding of nuclear factor-kappaB (band-shift assays) and phosphorylation of c-Jun and Jun N-terminal kinase (Western blots). In the kidney, interleukin-6 messenger RNA was increased, whereas Toll-like receptor 4 messenger RNA was significantly decreased. CONCLUSIONS: These results demonstrate that injection of peptidoglycan alone causes organ injury/dysfunction, organ inflammation, and systemic inflammation in the rat, involving nuclear factor-kappaB and possibly activator protein 1. These data support the contention that peptidoglycan is a contributing factor in the pathophysiology of organ injury in sepsis.
Authors: Yinzhong Zhang; Xinchun Lin; Kiyokazu Koga; Koichiro Takahashi; Helena M Linge; Adriana Mello; Teresina Laragione; Percio S Gulko; Edmund J Miller Journal: Mol Med Date: 2011-04-28 Impact factor: 6.354
Authors: Anders E Myhre; Jon Fredrik Stuestøl; Maria K Dahle; Gunhild Øverland; Christoph Thiemermann; Simon J Foster; Per Lilleaasen; Ansgar O Aasen; Jacob E Wang Journal: Infect Immun Date: 2004-03 Impact factor: 3.441