Phosphatidylcholine-specific phospholipase C, but not phospholipase D, is involved in pemphigus IgG-induced signal transduction.
The precise mechanism of the acantholysis after pemphigus IgGs bind to desmoglein (Dsg) 3 and/or Dsg 1 on the cell surface is as yet unknown. We have previously reported that pemphigus IgG (P-IgG) causes a transient increase in intracellular calcium and inositol 1,4,5-trisphosphate concentration, and subsequent activation of protein kinase C (PKC) in DJM-1 cells, a squamous cell carcinoma line. In order to see whether phosphatidylcholine (PC)-specific phospholipase C (PLC) or phospholipase D (PLD) is involved in the P-IgG-induced signaling process, the production of 1,2-diacylglycerol (DAG) and phosphatidylbutanol (PBut), a potential marker for the determination of PLD activity in the presence of butanol, was determined in DJM-1 cells. A biphasic accumulation of DAG, which consisted of a first transient phase and a second sustained phase, was observed. The second phase of DAG accumulation was profoundly inhibited by pretreatment with D609, a selective inhibitor of PC-PLC, but not by propranolol, an inhibitor of phosphatidate phosphohydrolase. Pemphigus serum after preadsortion of antibodies to Dsg 3 and Dsg 1 with recombinant Dsg 3 and Dsg 1 did not show formation of DAG. PBut was not generated following the addition of P-IgG. In addition, the levels of [3H]phosphocholine, a direct metabolite of PC-PLC, were elevated after the addition of P-IgG. These results suggest that the PC-PLC pathway plays a major role in P-IgG-induced transmembrane signaling by causing prolonged generation of DAG, which may lead to long-term activation of PKC.
Seishima
M
M
Department of Dermatology, Ogaki Municipal Hospital, Japan.
Iwasaki-Bessho
Y
Y
Itoh
Y
Y
Nozawa
Y
Y
Amagai
M
M
Kitajima
Y
Y
D001952:Bridged-Ring Compounds / Q000494:pharmacology; D004075:Diglycerides / Q000096:biosynthesis; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D009636:Norbornanes; D010392:Pemphigus / Q000276:immunology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010739:Phospholipase D / Q000502:physiology*; D010767:Phosphorylcholine / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000502:physiology*
D001952:Bridged-Ring Compounds; D004075:Diglycerides; D007074:Immunoglobulin G; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; D010767:Phosphorylcholine; C046498:tricyclodecane-9-yl-xanthogenate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D010739:Phospholipase D; D043265:Phosphatidylinositol Diacylglycerol-Lyase