Distribution pattern of matrix metalloproteinases 1, 2, 3, and 9, tissue inhibitors of matrix metalloproteinases 1 and 2, and alpha 2-macroglobulin in cases of generalized AA- and AL amyloidosis.
Matrix metalloproteinases (MMPs) degrade basement membranes and connective tissue and play an essential role in the homeostasis of the extracellular matrix which is disrupted by the deposition of amyloid. This immunohistochemical study investigated the distribution pattern of matrix metalloproteinases (MMP-1, -2, -3, and -9) and their inhibitors [alpha 2-macroglobulin (alpha 2-M), tissue inhibitors of MMPs (TIMP)-1, and TIMP-2] in human AA- and AL amyloid deposits. Specimens of liver, kidney, and spleen from 22 autopsy cases were investigated. Nine patients had suffered from generalized AA amyloidosis, eight from generalized AL amyloidosis, and five from rheumatoid arthritis or tuberculosis with no histological evidence of amyloid. In all amyloidotic and non-amyloidotic patients, each protease and protease inhibitor was detected in almost every organ investigated. In the amyloidotic cases, there was no indication that a specific protease or protease inhibitor was absent or expressed, but a difference was observed in their spatial distribution patterns. The most noticeable difference was found in immunostaining of amyloid. Only MMP-1, -2, and -3, and alpha 2-M were present in AA amyloid deposits, and only TIMP-1 and TIMP-2 were found in deposits of AL amyloid. This is the first study to show that MMP-1, -2, and -3 are present in AA amyloid deposits. They may be involved in tissue remodeling or in proteolysis of the precursor and fibril proteins.
Müller
D
D
Institute of Pathology, Otto-von-Guericke-University, Leipziger Str. 44, D-39120 Magdeburg, Germany.
Roessner
A
A
Röcken
C
C
D000328:Adult; D000368:Aged; D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000145:classification / Q000378:metabolism*; D005260:Female; D006801:Humans; D007158:Immunologic Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D013194:Staining and Labeling; D014018:Tissue Distribution; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism*
D000682:Amyloid; D019714:Tissue Inhibitor of Metalloproteinases; D000511:alpha-Macroglobulins; D020782:Matrix Metalloproteinases