Demonstration of plasma proteinase inhibitors in beta 2-microglobulin amyloid deposits.
beta 2-microglobulin-related amyloidosis (A beta 2M) represents a frequent complication in long-term dialysis patients. Although the pathogenetic mechanism has yet to be fully understood, it is known that amyloid fibrils usually consist of intact molecules of beta 2-microglobulin (beta 2m). Plasma proteinase inhibitors (PPI) are a broad family of glycoproteins with the function of eliminating unwanted proteolysis of serine proteases. Their role in amyloidogenesis has become a subject of intense discussion, especially since the recent identification of alpha 1-antichymotrypsin in the beta-protein amyloid deposits of Alzheimer's disease. We evaluated immunohistochemically and biochemically the presence and distribution of several PPIs (alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, antithrombin III, alpha 2-macroglobulin and tissue inhibitor metalloproteinase) and amyloid P component in A beta 2M deposits in osteo-articular and visceral tissues from dialysis patients with amyloidosis, as well as two carpal tunnel synovia from non-dialysis patients and one Alzheimer's brain as controls. The immunohistochemical study demonstrated that all but one (anti-alpha 1-antichymotrypsin) of the PPI antibodies tested showed varying degrees of positive reaction against A beta 2M deposits. All the antibodies (including anti-alpha 1-antichymotrypsin) also reacted to some extent with other non-amyloid visceral and connective tissue elements diffusely and/or selectively. Among them, only the reaction of anti-amyloid P component had significantly distinctive localization to A beta 2M deposits, which were identified in adjacent serial sections by Congo red staining and immunohistochemical reaction against anti-beta 2m.(ABSTRACT TRUNCATED AT 250 WORDS)
D000368:Aged; D000682:Amyloid / Q000032:analysis*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000032:analysis* / Q000097:blood; D019714:Tissue Inhibitor of Metalloproteinases; D000514:alpha 1-Antichymotrypsin / Q000097:blood; D000511:alpha-Macroglobulins / Q000032:analysis; D001613:beta 2-Microglobulin / Q000032:analysis*
D000682:Amyloid; D006023:Glycoproteins; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D000514:alpha 1-Antichymotrypsin; D000511:alpha-Macroglobulins; D001613:beta 2-Microglobulin