Table 2.

The pathophysiology of dialysis-related amyloidosis involves an inflammatory cascade and altered matrix metabolism

MediatorMechanism
FibroblastsInteractions with modified or unmodified B2M produce secretion of MCP-1 with monocyte attraction. MMP-3 leads to inflammation and tissue damage.
MonocytesAttracted by MCP-1, monocytes differentiate into macrophages and contribute to inflammation via enhanced cytokine production.
MMP-1 and MMP-3Proteinases, secreted by fibroblasts, produce cartilaginous injury by collagen and proteoglycan degradation.
AGE-modified B2MInteraction with fibroblast RAGE results in endocytosis and transcription of genes involved in the inflammatory response.
Unmodified B2MInteracts with fibroblasts resulting in MMP-1 secretion.
IL-1β, TNF-αCytokines involved in the inflammatory response to B2M.
TGF-βCytokine found in amyloid deposits and has chemotactic activity for monocytes. Inhibits macrophage IL-1β and TNF-α.
  • The principal participants are described. B2M, β-2 microglobulin; MCP-1, monocyte chemoattractant peptide-1; MMP-3, matrix metalloproteinase-3; AGE, advanced glycation end products; RAGE, receptor for AGE.