Atwa MA, Smallridge RC, Burch HB, Gist ID, Lu R, Abo-Hashem EM, El-Kannishy MH, Burman KD. Immunoglobulins from Graves' disease patients stimulate phospholipase A2and C systems in FRTL-5 and human thyroid cells. Eur J Endocrinol 1996;135:322–7. ISSN 0804–4643We 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 μg/ml)-induced AA release in FRTL-5 thyroid cells. U-73122 (3 μmol/l), a PLC inhibitor, and quinacrine (100 μmol/l) but not U-26384 (5 μmol/l), PLA2inhibitors, blocked the IgG-induced (20 μg/ml) AA release in FRTL-5 thyroid cells. Immunoglobulin G (100 μg/ml) also stimulated accumulation of inositol-1,4,5-triphosphate (IP3) in a time- and dose-dependent (20–300 μg/ml) manner in FRTL-5 cells. Immunoglobulin G from Graves' disease patients induced a significant increase of IP3production (p = 0.01) compared to IgG from normal subjects. Removal of external calcium had no significant effect on the IgG-induced IP3production. The PLC inhibitor U-73122 completely blocked IgG-induced IP3production 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 IP3production (p = 0.004) compared to the IgG from normal subjects. These data indicate that IgG from Graves' disease patients induced PLA2activity that was PLC dependent, a pattern referred to as sequential activation. Our studies suggest that IgG from Graves' disease patients activates PLA2and 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.Kenneth D Burman, Endocrine Section, Washington Hospital Center, 110 Irving St. NW, Washington, DC 20010, USA