Apoptosis Is the Mechanism Associated with Mesangial Cell Deletion In Monoclonal Light Chain-Related Renal Diseases
GA Herrera, EA Turbat-Herrera, J Teng. Bostwick Laboratories- Nephrocor, Tempe, AZ; Saint Louis University, St. Louis, MO
Background: The glomerular pathology in light chain deposition disease (LCDD) and AL (light chain-associated)-amyloidosis in its advanced stage is characterized by a loss of mesangial cells. The mechanisms involved in this process have not been completely elucidated. This study was conducted to evaluate the role of apoptosis in cell deletion in these diseases.
Design: Rat mesangial cells were incubated with light chains obtained and purified from the urine of patients with LCDD and AL-amyloidosis (10 ug/ml) for periods up to 6 weeks (n=6). Mesangial cell apoptosis was monitored using several techniques including light, electron and scanning electron microscopy, caspase 3 activation, annexin V expression on cell membranes, and propidium iodine to identify DNA changes associated with the apoptotic process. Curcumin was added to experimental conditions to evaluate if it had any effects on apoptosis.
Results: Apoptosis was significantly increased over controls when mesangial cells were incubated with both LCDD and AL-light chains. Apoptosis was more pronounced in mesangial cells treated with AL-light chains (approximately 2 times more) than with LCDD-light chains. The correlation between nuclear changes and cytosol / membranous alterations typically associated with apoptosis was excellent. Curcumin enhanced the apoptotic effect of both glomerulopathic light chains (almost 3 fold each). When rat mesenchymal stem cells were coincubated with rat mesangial cells and trated with glomerulopathic light chains, the apoptotic effect increased as well and the replacement of injured mesangial cells by mesenchymal stem cells occurred faster. Classical morphological findings were noted by routine and scanning EM in apoptotic mesangial cells.
Conclusions: Apoptosis represents the mechanism of cell deletion associated with the glomerular damage that occurs in LCDD and AL-amyloidosis. This explains the morphologic findings seen in glomeruli affected by these conditions, where in the advanced stage mesangial cells are few and extracellular matrix and amyloid fibrils respectively represent the main components of the expanded mesangium. If apoptosis is enhanced, the repair mechanism and replacement of injured mesangial cells by mesenchymal stem cells occurs faster.
Category: Kidney (does not include tumors)
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 193, Tuesday Afternoon