Immunoglobulins from Graves' disease patients stimulate phospholipase A2 and C systems in FRTL-5 and human thyroid cells.
We have studied the effects of immunoglobulin G from Graves' disease patients on phospholipase A2 (PLA2) and C(PLC) systems in FRTL-5 and human thyroid cells. Immunoglobulin G (IgG) from Graves' disease patients stimulated arachidonic acid (AA) release in a time- and dose-dependent manner. In FRTL-5 thyroid cells, removal of external calcium had no significant effect on the IgG (20 micrograms/ml)-induced AA release in FRTL-5 thyroid cells. U-73122 (3 mumol/l), a PLC inhibitor, and quinacrine (100 mumol/l) but not U-26384 (5 mumol/l), PLA2 inhibitors, blocked the IgG-induced (20 micrograms/ml) AA release in FRTL-5 thyroid cells. Immunoglobulin G (100 micrograms/ml) also stimulated accumulation of inositol-1,4,5-triphosphate (IP3) in a time- and dose-dependent (20-300 micrograms/ml) manner in FRTL-5 cells. Immunoglobulin G from Graves' disease patients induced a significant increase of IP3 production (p = 0.01) compared to IgG from normal subjects. Removal of external calcium had no significant effect on the IgG-induced IP3 production. The PLC inhibitor U-73122 completely blocked IgG-induced IP3 production from FRTL-5 thyroid cells. Also, in human thyroid cells, IgG from Graves' disease patients induced a significant increase of AA release (p = 0.001) and IP3 production (p = 0.004) compared to the IgG from normal subjects. These data indicate that IgG from Graves' disease patients induced PLA2 activity that was PLC dependent, a pattern referred to as sequential activation. Our studies suggest that IgG from Graves' disease patients activates PLA2 and PLC systems in FRTL-5 and human thyroid cells. These signal transduction pathways could be involved in the pathogenesis of Graves' disease and future studies are warranted to investigate this area.
Endocrine Section, Washington Hospital Center, Medlantic Research Institute, George Washington University Medical Center, Washington, DC, USA.
M A
MA
Atwa
R C
RC
Smallridge
H B
HB
Burch
I D
ID
Gist
R
R
Lu
E M
EM
Abo-Hashem
M H
MH
el-Kannishy
K D
KD
Burman
D000328:Adult; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D006111:Graves Disease / Q000097:blood*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects* / Q000201:enzymology*; D010738:Type C Phospholipases / Q000378:metabolism*
D007074:Immunoglobulin G; D016718:Arachidonic Acid; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases