In vitro modulation of AL-amyloid formation by human mesangial cells exposed to amyloidogenic light chains.
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-beta 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-beta, 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-beta, 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-beta 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-beta and sTSP modulate in vitro AL-amyloidosis.
Isaac
J
J
Department of Pathology, Louisiana State University Medical Center, Shreveport, LA 71130, USA.
Kerby
J D
JD
Russell
W J
WJ
Dempsey
S C
SC
Sanders
P W
PW
Herrera
G A
GA
D000682:Amyloid / Q000096:biosynthesis* / Q000302:isolation & purification / Q000652:urine; D000686:Amyloidosis / Q000652:urine; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D007674:Kidney Diseases / Q000652:urine; D007684:Kidney Tubules / Q000473:pathology; D019699:Thrombospondins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000682:Amyloid; D007147:Immunoglobulin Light Chains; D019699:Thrombospondins; D016212:Transforming Growth Factor beta; D002738:Chloroquine