Cellular localization of matrix metalloproteinases in the abdominal aortic aneurysm wall.
OBJECTIVE
This study explores the source(s) of the matrix-degrading proteinases, matrix metalloproteinase 1 (MMP-1; interstitial collagenase), matrix metalloproteinase 3 (MMP-3; stromelysin 1), and matrix metalloproteinase 9 (MMP-9; gelatinase B), previously implicated in abdominal aortic aneurysm (AAA) development. The possible involvement of the plasmin cascade in the activation of these proteinases was also explored by examining the presence of the urokinase-type plasminogen activator (uPA) in aneurysm wall.


METHODS
Immunohistochemical techniques were used to detect the presence of MMP-1, MMP-3 and MMP-9 proteins and uPA in fixed, paraffin-embedded tissue sections from AAA (n = 10) and control (n = 2) aortas.


RESULTS
The MMP-9 protein was localized to mononuclear cells in the AAA wall. Dual-labeling techniques confirmed the identity of these cells as macrophages. The MMP-3 protein and uPA were also detected primarily in the macrophage-like mononuclear cells infiltrating the aneurysmal aorta. Immunoreactive material to MMP-1 was demonstrated in mesenchymal cells of the AAA wall suggesting alternative expression and delivery of this enzyme in AAA.


CONCLUSIONS
This work establishes the role of macrophages in the delivery, expression, and possible activation of matrix destructive proteinases during AAA pathogenesis and suggests a role for the activation of MMPs in the progression of the disease.
Newman
K M
KM
Department of Surgery, St. Lukes/Roosevelt Hospital Center, New York, NY 10019.
Jean-Claude
J
J
Li
H
H
Scholes
J V
JV
Ogata
Y
Y
Nagase
H
H
Tilson
M D
MD
D000911:Antibodies, Monoclonal; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000473:pathology; D017364:Collagenases / Q000378:metabolism*; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D013194:Staining and Labeling; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1