Immunoglobulin light chain alters mesangial cell calcium homeostasis.
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.
Zhu
L
L
Department of Pathology, University of Alabama at Birmingham, 35294-0007, USA.
Herrera
G A
GA
White
C R
CR
Sanders
P W
PW
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000302:isolation & purification / Q000494:pharmacology* / Q000652:urine; D007294:Inositol / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D009101:Multiple Myeloma / Q000276:immunology / Q000652:urine; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
D007145:Immunoglobulin kappa-Chains; D007294:Inositol; D004533:Egtazic Acid; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D002118:Calcium