PMID- 10036581
OWN - NLM
STAT- MEDLINE
DCOM- 19990428
LR  - 20191102
IS  - 1350-6129 (Print)
IS  - 1350-6129 (Linking)
VI  - 5
IP  - 4
DP  - 1998 Dec
TI  - In vitro modulation of AL-amyloid formation by human mesangial cells exposed to 
      amyloidogenic light chains.
PG  - 238-46
AB  - 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.
FAU - Isaac, J
AU  - Isaac J
AD  - Department of Pathology, Louisiana State University Medical Center, Shreveport, 
      LA 71130, USA.
FAU - Kerby, J D
AU  - Kerby JD
FAU - Russell, W J
AU  - Russell WJ
FAU - Dempsey, S C
AU  - Dempsey SC
FAU - Sanders, P W
AU  - Sanders PW
FAU - Herrera, G A
AU  - Herrera GA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - Amyloid
JT  - Amyloid : the international journal of experimental and clinical investigation : 
      the official journal of the International Society of Amyloidosis
JID - 9433802
RN  - 0 (Amyloid)
RN  - 0 (Immunoglobulin Light Chains)
RN  - 0 (Thrombospondins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 886U3H6UFF (Chloroquine)
SB  - IM
MH  - Amyloid/*biosynthesis/isolation & purification/urine
MH  - Amyloidosis/urine
MH  - Cells, Cultured
MH  - Chloroquine/pharmacology
MH  - Glomerular Mesangium/cytology/*metabolism
MH  - Humans
MH  - Immunoglobulin Light Chains/isolation & purification/*metabolism/urine
MH  - Kidney Diseases/urine
MH  - Kidney Tubules/pathology
MH  - Thrombospondins/pharmacology
MH  - Transforming Growth Factor beta/pharmacology
EDAT- 1999/02/26 00:00
MHDA- 1999/02/26 00:01
CRDT- 1999/02/26 00:00
PHST- 1999/02/26 00:00 [pubmed]
PHST- 1999/02/26 00:01 [medline]
PHST- 1999/02/26 00:00 [entrez]
AID - 10.3109/13506129809007296 [doi]
PST - ppublish
SO  - Amyloid. 1998 Dec;5(4):238-46. doi: 10.3109/13506129809007296.