Peptidoglycan of S. aureus causes increased levels of matrix metalloproteinases in the rat.
Matrix metalloproteinases (MMPs) have been suggested to contribute to the organ injury in septic patients. We recently demonstrated that peptidoglycan (PepG) of S. aureus causes organ injury in the rat. A possible role for MMPs in the septic response to PepG is unknown. In the present study, we have examined whether the release of MMP-9 (gelatinase B) and MMP-2 (gelatinase A) is induced by PepG in the anesthetized rat. Male Wistar rats were injected intravenously with PepG (10 mg/kg), LPS (1 mg/kg), or a combination of LPS and PepG (1 mg/kg of each). After 1 or 3 h, liver, lung, and plasma were harvested. MMP-9 and MMP-2 levels were analyzed in organ homogenates and in plasma samples by zymography. MMP-9 levels were significantly increased in the lung within 1 h after injection of PepG, LPS, or combined treatment, compared with sham animals (P < or = 0.05). In the liver and plasma, MMP-9 was clearly increased by PepG or LPS at both 1 and 3 h compared with sham animals (P < or = 0.05). Considerable basal amounts of MMP-2 protein were seen in the liver and in plasma. In the lung, MMP-2 levels were elevated by combined LPS/PepG at 1 h and by LPS at 3 h (P < or = 0.05). In contrast, MMP-2 activity in the liver was significantly reduced by bacterial products. In the plasma, no major alterations of MMP-2 levels were observed. Our data show that PepG of S. aureus causes a rapid elevation of MMP-9 protein in the liver, lung, and blood of the rat. Based on these and previous data, we hypothesize that the release of MMP-9 in lung, liver, and blood is part of the septic host response to systemic PepG.
Wang
Jacob E
JE
Institute for Surgical Research, Rikshospitalet University Hospital, Oslo, Norway. jacob.wang@klinmed.uio.no
Pettersen
Solveig
S
Stuestol
Jon Fredrik
JF
Wang
Yun Yong
YY
Foster
Simon J
SJ
Thiemermann
Christoph
C
Aasen
Ansgar O
AO
Bjørnland
Kristin
K
D000818:Animals; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects* / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000378:metabolism*; D010457:Peptidoglycan / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013211:Staphylococcus aureus
D008070:Lipopolysaccharides; D010457:Peptidoglycan; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9