PMID- 11351041
OWN - NLM
STAT- MEDLINE
DCOM- 20010607
LR  - 20230216
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 81
IP  - 5
DP  - 2001 May
TI  - Monoclonal light chain--mesangial cell interactions: early signaling events and 
      subsequent pathologic effects.
PG  - 689-703
AB  - Glomerulopathic monoclonal light chains (G-LC) interact with mesangial cells 
      (MC), resulting in alterations of mesangial homeostasis. Early signaling events 
      control mitogenic activities and cytokine production, which in turn participate 
      in the subsequent pathologic events. Mesangial homeostasis is affected in two 
      very different ways, depending on whether the G-LC is from a patient with light 
      chain deposition disease (LCDD) or light chain-related amyloidosis (AL-Am). In 
      contrast, tubulopathic (T)-LC chains from patients with myeloma cast nephropathy 
      do not significantly interact with MC and result in no alterations in mesangial 
      homeostasis. Therefore, understanding early events in the monoclonal LC-MC 
      interactions is fundamental. MC in culture were exposed to LC obtained and 
      purified from the urine of patients with plasma cell dyscrasias and biopsy-proven 
      renal disease, including LCDD, AL-Am, and myeloma cast nephropathy. Incubation of 
      MC with G-LC, but not T-LC, resulted in cytoskeletal and cell shape changes, 
      activation of platelet-derived growth factor-beta (PDGF-beta) and its 
      corresponding receptor, cytoplasmic to nuclear migration of c-fos and NF-kappa 
      beta signals, and production of monocyte chemoattractant protein-1 (MCP-1), as 
      well as increased expression of Ki-67, a proliferation marker. Although NF-kappa 
      beta activation was directly related to MCP-1 production, c-fos activation 
      regulated proliferative signals and cytoskeletal changes in MC. Amyloidogenic LC 
      were avidly internalized by the MC, whereas LCDD-LC effector targets were located 
      at the MC surface. These cellular events are likely initiated as a result of 
      interactions of the G-LC with yet-uncharacterized MC surface receptors. 
      Dissecting the events taking place when G-LC interact with MC may define 
      potential important targets for selective therapeutic manipulation to ameliorate 
      or prevent the glomerular injury that ensues.
FAU - Russell, W J
AU  - Russell WJ
AD  - Department of Pathology, Louisiana State University Health Sciences Center, 
      Shreveport, Louisiana 71130, USA.
FAU - Cardelli, J
AU  - Cardelli J
FAU - Harris, E
AU  - Harris E
FAU - Baier, R J
AU  - Baier RJ
FAU - Herrera, G A
AU  - Herrera GA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Chemokine CCL2)
RN  - 0 (Immunoglobulin Light Chains)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Amyloidosis/urine
MH  - Animals
MH  - Blotting, Western
MH  - CHO Cells
MH  - Carcinoma, Renal Cell/urine
MH  - Cells, Cultured
MH  - Chemokine CCL2/analysis
MH  - Cricetinae
MH  - Flow Cytometry
MH  - Glomerular Mesangium/cytology/*immunology/ultrastructure
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Immunoglobulin Light Chains/*immunology/isolation & purification
MH  - Immunohistochemistry
MH  - Ki-67 Antigen/analysis
MH  - Kidney Neoplasms/urine
MH  - L Cells
MH  - Mice
MH  - NF-kappa B/analysis
MH  - Nephrectomy
MH  - Nuclear Proteins/analysis
MH  - Proto-Oncogene Proteins c-fos/analysis
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/analysis
EDAT- 2001/05/15 10:00
MHDA- 2001/06/08 10:01
CRDT- 2001/05/15 10:00
PHST- 2001/05/15 10:00 [pubmed]
PHST- 2001/06/08 10:01 [medline]
PHST- 2001/05/15 10:00 [entrez]
AID - S0023-6837(22)01958-4 [pii]
AID - 10.1038/labinvest.3780278 [doi]
PST - ppublish
SO  - Lab Invest. 2001 May;81(5):689-703. doi: 10.1038/labinvest.3780278.