Interaction between beta 2-microglobulin and advanced glycation end products in the development of dialysis related-amyloidosis.
Dialysis related amyloidosis (DRA) is a progressive debilitating complication of long-term dialysis. beta 2-microglobulin (beta 2m) amyloid deposition occurs preferentially in older patients and initially is located in collagen-rich osteo-articular tissues. Since an age-dependent increase in the formation of advanced glycation end products (AGE) has been observed in collagen-containing structures, we hypothesized that AGE-modified beta 2m in the amyloid of DRA may be formed locally in osteo-articular structures as a subsequent event of its binding to collagen-AGE. Based on this hypothesis, we investigated the binding between beta 2m and AGE-modified collagen (collagen-AGE) in vitro. Significantly larger amounts of human beta 2m were bound to types I to IV of immobilized collagen-AGE than to unmodified collagens (P < 0.0001). The quantity of beta 2m bound to collagen-AGE was dependent on the concentrations of both beta 2m and of AGE contained in collagen (P < 0.01). Unmodified beta 2m was more avidly bound to collagen-AGE or collagen in comparison to AGE-modified beta 2m (P < 0.0001). beta 2m bound to collagen-AGE could be modified further by nonenzymatic glycosylation during three weeks of incubation with physiologic concentrations of glucose. Similar processes in vivo may be important in the pathobiology of DRA.
Hou
F F
FF
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Chertow
G M
GM
Kay
J
J
Boyce
J
J
Lazarus
J M
JM
Braatz
J A
JA
Owen
W F
WF
D000686:Amyloidosis / Q000209:etiology*; D003094:Collagen / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications; D006435:Renal Dialysis / Q000009:adverse effects*; D001613:beta 2-Microglobulin / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D001613:beta 2-Microglobulin; D003094:Collagen