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 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.
  • Keywords

  • Adenosine Triphosphate, Animals, Aorta, Calcium, Cells, Cultured, Egtazic Acid, Glomerular Mesangium, Homeostasis, Humans, Immunoglobulin kappa-Chains, Inositol, Kidney Cortex, Kinetics, Male, Multiple Myeloma, Muscle, Smooth, Vascular, Rats, Rats, Sprague-Dawley, Thapsigargin, Time Factors
  • Digital Object Identifier (doi)

    Pubmed Id

  • 19449051
  • Author List

  • Zhu L; Herrera GA; White CR; Sanders PW
  • Start Page

  • F319
  • End Page

  • F324
  • Volume

  • 272
  • Issue

  • 3 Pt 2