What are the cellular and extracellular tissue factors in the pathophysiology of AA (inflammatory) amyloidosis?

Updated: Jan 08, 2021
  • Author: Jefferson R Roberts, MD; Chief Editor: Herbert S Diamond, MD  more...
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Answer

Cellular and extracellular tissue factors :

Mononuclear phagocytes might play a role in degradation of SAA and initiation of development of AA amyloidosis.

Polymorphisms of the mannose-binding lectin 2(MBL-2) gene leading to decreased levels of functional MBL have been related to defective macrophage function. This suggests that genetic background may affect the ability of mononuclear phagocytes to effectively process and degrade SAA proteins.

Additional tissue factors, such as enzymes found in the extracellular matrix, are likely to be involved in the proteolytic processing of SAA. Matrix metalloproteinases (MMPs) are involved in generation of SAA N-terminal fragments. In vitro studies confirmed that human SAAs and AA amyloid fibrils are susceptible to proteolytic cleavage by MMPs, generating fragments of different sizes. Studies have demonstrated that susceptibility to MMP-1 degradation is highly dependent on SAA1 genotype. [10]

The factors responsible for determining the site of deposition in any form of amyloidosis have not been identified. AA fibrils have been generated in tissue cultures by incubating SAA with macrophages. Deposits are frequently found in tissues with large numbers of phagocytic cells, notably the liver and spleen, but other affected organs, such as the kidneys, do not have the same cellular composition. Some data, derived from analysis of renal biopsy specimens, have suggested that glycoxidative modification of proteins, probably the AA protein itself, may also play a role in AA deposition in kidneys.


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