In vitro modulation of AL-amyloid formation by human mesangial cells exposed to amyloidogenic light chains

• Published in: Amyloid 1998, Vol.5 (4), p.238-246
• Main Authors: Isaac, Jorge, Kerby, Jeff D., Russell, William J., Dempsey, Susanna C., Sanders, Paul W., Herrera, Guillermo A.
• Format: Article
• Language: English
• Subjects: Amyloid - biosynthesis; Amyloid - isolation & purification; Amyloid - urine; Amyloidogenic light chain; Amyloidosis - urine; Cells, Cultured; Chloroquine - pharmacology; Glomerular Mesangium - cytology; Glomerular Mesangium - metabolism; Humans; Immunoglobulin Light Chains - isolation & purification; Immunoglobulin Light Chains - metabolism; Immunoglobulin Light Chains - urine; in vitro AL-amyloidosis; Kidney Diseases - urine; Kidney Tubules - pathology; mesangial cells; Thrombospondins - pharmacology; Transforming Growth Factor beta - pharmacology
• ISSN: 1350-6129; 1744-2818
• DOI: 10.3109/13506129809007296

We have shown in vitro AL-amyloid formation by human mesangial cells (HMCs). AL-amyloid formation may require lysosomal processing of the light chains (LCs) by HMCs for amyloidogenesis to occur. Chloroquine inhibits lysosomal activity. TGF-β mediates extracellular matrix formation in many glomerulopathies. Thrombospondin (TSP) has been proposed as a mediator of cell proliferation and a marker of early fibrosis. We investigated amyloid formation by HMCs exposed to AL-LCs in the absence of amyloid enhancing factor (AEF). The effects of TGF-β, TSP and chloroquine on in vitro amyloid formation were studied. HMCs were incubated with two AL-LCs, a light chain deposition disease (LCDD)-LC, or one of two tubulopathic LCs (T-LCs). Additional cells were treated with an AL-LC and chloroquine, TGF-β, or TSP. Amyloid formation was evaluated microscopically using hematoxylin and eosin, Congo red and Thioflavin-T stains, as well as ultrastructurally. Amyloid was formed only when HMCs were incubated with AL-LCs. Addition of TSP significantly enhanced amyloid formation. In contrast, exogenous TGF-β and chloroquine significantly attenuated amyloid formation. These findings show that some AL-LCs do not require AEF for amyloidogenesis to occur, and that chloroquine, TGF-β and sTSP modulate in vitro AL-amyloidosis.