Collagenase 2/matrix metalloproteinase 8 in critically ill patients with secondary peritonitis.
Secondary peritonitis is an important indication for surgical intensive care admissions, and it is associated with high morbidity and mortality. Collagenase 2/matrix metalloproteinase (MMP) 8 is a tissue matrix-degrading enzyme that is released from leukocytes upon inflammatory stimuli and may thus contribute to peritonitis-associated organ damage. We studied the levels and activity of MMP-8 in the peritoneal fluid of 15 critically ill patients with secondary peritonitis. The MMP-8 levels were measured from the patients' peritoneal fluid, serum, and urine, and from the serum and urine of 10 healthy controls by immunofluorometric assay. Median MMP-8 level in peritoneal fluid supernatant was 1,317 microg/L (interquartile range [IQR]) (1,254-1,359 microg/L) being significantly higher than in the sera of the patients (P=0.008). Molecular forms and isoform distribution of MMP-8, MMP-1, and MMP-13 in peritoneal fluid, assessed by Western immunoblotting, revealed that the neutrophil-type MMP-8 was the major collagenase species in peritoneal fluid, and it was partially in an activated form. Catalytically competent, active MMP-8 produced the characteristic cleavage products from intact human type I collagen. The serum levels of MMP-8 were higher in the patients, 49 microg/L (IQR, 23-214 microg/L), than in the controls, 11 microg/L (IQR, 8-24 microg/L) (P<0.01). The MMP-8 levels in the urine were higher in the patients, 0.27 microg/L (IQR, 0.04-1.89 microg/L), than in the controls, 0.03 microg/L (IQR, 0.0-0.05 microg/L) (P=0.013). Our data demonstrate for the first time that MMP-8 levels are remarkably elevated and in an active and catalytically competent form in the peritoneal fluid samples of patients with secondary peritonitis.
Hästbacka
Johanna
J
Division of Anesthesiology and Intensive Care Medicine, Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland. johanna.hastbacka@kolumbus.fi
Hynninen
Marja
M
Kolho
Elina
E
Pettilä
Ville
V
Tervahartiala
Taina
T
Sorsa
Timo
T
Lauhio
Anneli
A
D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000201:enzymology*; D016638:Critical Illness; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000097:blood / Q000652:urine; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000032:analysis* / Q000097:blood / Q000652:urine; D008875:Middle Aged; D010538:Peritonitis / Q000097:blood / Q000201:enzymology* / Q000209:etiology / Q000652:urine
D007527:Isoenzymes; D020784:Matrix Metalloproteinase 8