title: Peptidoglycan of S. aureus causes increased levels of matrix metalloproteinases in the rat.
abstract: 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.
authors.affiliation: Institute for Surgical Research, Rikshospitalet University Hospital, Oslo, Norway. jacob.wang@klinmed.uio.no
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Wang
authors.forename: Solveig
authors.initials: S
authors.lastname: Pettersen
authors.forename: Jon Fredrik
authors.initials: JF
authors.lastname: Stuestol
authors.forename: Yun Yong
authors.initials: YY
authors.lastname: Wang
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foster
authors.forename: Christoph
authors.initials: C
authors.lastname: Thiemermann
authors.forename: Ansgar O
authors.initials: AO
authors.lastname: Aasen
authors.forename: Kristin
authors.initials: K
authors.lastname: Bjørnland
mesh_terms: 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
chemical_list: D008070:Lipopolysaccharides; D010457:Peptidoglycan; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9