AJP - Renal Physiology, Vol 272, Issue 3 319-F324, Copyright © 1997 by American Physiological Society
Immunoglobulin light chain alters mesangial cell calcium homeostasis
L. Zhu, G. A. Herrera, C. R. White and P. W. Sanders
Department of Pathology, University of Alabama at Birmingham, 35294-0007, USA.
This study examined the hypothesis that certain immunoglobulin light chains
directly altered mesangial cell calcium homeostasis. Intracellular Ca2+
concentration (intracellular [Ca2+]) signaling was determined in
suspensions of rat mesangial cells using the acetoxymethyl ester of fura 2
with a calcium removal/replacement protocol. Pretreatment of cultured rat
mesangial cells with a glomerulopathic kappa-light chain (gle) produced
reversible dose- and time-dependent attenuation of ATP- and thrombin-evoked
[Ca2+] transients (189 +/- 24 vs. 126 +/- 10 nM, P < 0.05 with ATP; 198
+/- 5 vs. 117 +/- 3 nM, P < 0.05 with thrombin) and capacitative calcium
influx (199 +/- 14 vs. 142 +/- 17 nM, P < 0.05 for ATP; 252 +/- 19 vs.
198 +/- 18 nM, P < 0.05 for thrombin). Mesangial cells treated with gle
and supplemented with myo-inositol (450 microM) did not demonstrate the
attenuation of the ATP-evoked [Ca2+] transient and capacitative calcium
influx. Gle also decreased mean [Ca2+] transient (80 +/- 7 vs. 56 +/- 1 nM,
P < 0.05) and capacitative calcium influx (306 +/- 10 vs. 241 +/- 4 nM,
P < 0.05) in response to thapsigargin, a Ca2+-adenosinetriphosphatase
inhibitor. This inhibition was not reversed by exogenous myo-inositol.
Another kappa-light chain (10 microg/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.
