Immunoglobulin light chain alters mesangial cell calcium homeostasis

Academic Article

Abstract

  • 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 κ-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-inosital (450 μM) 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 inhibition. This inhibition was not reversed by exogenous myo-inositol. An-other κ-light chain (10 μg/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.
  • Pubmed Id

  • 7085779
  • Author List

  • Zhu L; Herrera GA; White CR; Sanders PW
  • Volume

  • 272
  • Issue

  • 3 41-3