Assessment of serum matrix metalloproteinases MMP-2 and MMP-9 after human liver transplantation: increased serum MMP-9 level in acute rejection.
BACKGROUND
Alterations in synthesis and breakdown of extracellular matrix components play a role in acute rejection after orthotopic liver transplantation (OLT). Matrix metalloproteinases (MMPs) are capable of degrading basement membranes and are involved in the process of tissue remodelling in inflammation and liver fibrosis.


METHODS
We examined MMP-2 and MMP-9 in serum of 33 patients before and during 1 year after OLT, in 60 controls as well as in some specimens of cirrhotic liver and control liver tissue.


RESULTS
Serum MMP-2 levels before OLT were significantly higher compared with controls and decreased approximately 50% after OLT. Also, the MMP-2 content of cirrhotic liver specimens was significantly higher compared with normal liver. MMP-9 in serum and liver tissue of patients were similar to controls, but serum levels showed a peak at 1 week after OLT. At this time-point, total and active/inhibitor-complexed MMP-9 was significantly higher in patients with rejection (n=13) compared with those without rejection (n=20). The relative amount of MMP-9 in the active/inhibitor-complexed form did not differ between each group over time. Immunohistochemical staining at 1 week after OLT showed increased numbers of MMP-9-positive inflammatory cells in the portal triads of patients with rejection.


CONCLUSIONS
Patients with acute allograft rejection have elevated serum levels of MMP-9 1 week after OLT, which was most likely derived from inflammatory cells. An increased MMP-2 serum level and liver tissue content was found in patients with cirrhosis, which decreased after OLT. These observations indicate active involvement of MMP-2 and -9 in end-stage liver disease and OLT.
Kuyvenhoven
Johan Ph
JP
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
Verspaget
Hein W
HW
Gao
Qiang
Q
Ringers
Jan
J
Smit
Vincent T H B M
VT
Lamers
Cornelis B H W
CB
van Hoek
Bart
B
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000201:enzymology / Q000601:surgery; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000201:enzymology*; D006505:Hepatitis / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000201:enzymology; D008103:Liver Cirrhosis / Q000097:blood / Q000201:enzymology / Q000601:surgery; D008113:Liver Neoplasms / Q000097:blood / Q000201:enzymology / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D011184:Postoperative Period; D013194:Staining and Labeling
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9