Basic fibroblast growth factor-heparan sulphate complex in the human dialysis-related amyloidosis.
A major constituent of the amyloid fibrils in dialysis-related amyloidosis is beta 2-microglobulin (beta 2-MG). Heparan sulphates (HS) co-localize with the amyloid fibrils and monocytes/macrophages are commonly found around amyloid deposits, but the role of HS in amyloidogenesis is not yet defined. HS have variable saccharide sequences and can interact specifically with basic fibroblast growth factor (bFGF), a potent chemotactic factor for the monocyte/macrophage. The present investigation was undertaken to look for a functional link between co-localized HS and the pathogenesis of dialysis-related amyloidosis. Using amyloid-enriched ligament, immunohistochemical localization was tested for beta 2-MG, endogenous bFGF, and bFGF-binding portions of HS. For the detection of bFGF-binding portions of HS, the ligament sections were incubated with exogenous bFGF and then with anti-bFGF antibody. The specificity of the interaction between bFGF and HS was established by confirming a concomitant loss of immunoreactivity during selective removal of HS with heparitinase. beta 2-MG, endogenous bFGF, and bFGF-binding portions of HS were detected between bundles of collagen. Endogenous bFGF and bFGF-binding portions of HS were not detected in more advanced amyloid lesions, whereas beta 2-MG and other portions of HS were detected. We propose that beta 2-MG, endogenous bFGF, and bFGF-binding portions of HS form a complex and localize in the early amyloid lesions of dialysis-related amyloidosis.
Department of Internal Medicine, Branch Hospital of Nagoya University, School of Medicine, Japan.
H
H
Morita
T
T
Shinzato
Z
Z
Cai
G
G
David
A
A
Mizutani
H
H
Habuchi
M
M
Ito
J
J
Asai
K
K
Isobe
H
H
Yamada
D000686:Amyloidosis / Q000209:etiology; D001665:Binding Sites; D016222:Fibroblast Growth Factor 2 / Q000032:analysis* / Q000378:metabolism; D006497:Heparan Sulfate / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008022:Ligaments / Q000737:chemistry*; D006435:Renal Dialysis / Q000009:adverse effects*; D001613:beta 2-Microglobulin / Q000032:analysis / Q000378:metabolism
D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D001613:beta 2-Microglobulin