Immunoglobulin light chain alters mesangial cell calcium
homeostasis.
Zhu, Ling, Guillermo A. Herrera, C. Roger White, Paul W. Sanders.
Departments of Pathology, Medicine and Physiology, Nephrology
Research and Training Center, Comprehensive Cancer Center and the
Cell Adhesion and Matrix Research Center, University of Alabama at
Birmingham, Veterans Affairs Medical Center, Birmingham, AL, and
Department of Pathology, Louisiana State University Medical Center,
Shreveport, LA
APStracts 3:0214F, 1996.
This study examined the hypothesis that certain immunoglobulin light
chains directly altered mesangial cell calcium homeostasis.
Intracellular [Ca2&] signaling was determined in suspensions of
rat mesangial cells using Fura-2AM with a calcium removal/addback
protocol. Pre-treatment of cultured rat mesangial cells with a
glomerulopathic k light chain (gle) produced reversible dose- and
time-dependent attenuation of ATP- and thrombin-evoked [Ca2&]
transients (189+/-24 nM vs 126+/-10 nM, p<0.05 with ATP; 198+/-5
nM vs 117+/-3 nM, p<0.05 with thrombin) and capacitative calcium
influx (199+/-14 nM vs 142+/-17 nM, p<0.05 for ATP; 252+/-19 nM vs
198+/-18 nM, p<0.05 for thrombin). Mesangial cells treated with
gle and supplemented with myo-inositol (450 [mu]M) did not
demonstrate the attenuation of the ATP-evoked [Ca2&] transient
and capacitative calcium influx. Gle also decreased mean [Ca2&]
transient (80+/-7 nM vs 56+/-1 nM, p<0.05) and capacitative
calcium influx (306+/-10 nM vs 241+/-4 nM, p<0.05) in response to
thapsigargin, a Ca2& ATPase inhibitor. This inhibition was not
reversed by exogenous myo-inositol. Another k light chain (10
[mu]g/ml) did not affect mesangial cell calcium signaling. Deranged
mesangial cell calcium homeostasis by certain light chains may play a
central pathogenetic role in glomerulosclerosis associated with
deposition of immunoglobulin light chains.
Received 8 May 1996; accepted in final form 12 November 1996.
APS Manuscript Number F139-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996