Phosphatidylcholine-specific phospholipase C, but not phospholipase D, is involved in pemphigus IgG-induced signal transduction.

Abstract

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.

• Authors: M Seishima, Y Iwasaki-Bessho, Y Itoh, Y Nozawa, M Amagai, Y Kitajima
• Journal: Archives of dermatological research (Arch Dermatol Res) Vol. 291 Issue 11 Pg. 606-13 (Nov 1999) ISSN: 0340-3696 [Print] Germany
• PMID: 10638334 (Publication Type: Journal Article)

Chemical References

• Bridged-Ring Compounds
• Diglycerides
• Immunoglobulin G
• Norbornanes
• Thiocarbamates
• Thiones
• Phosphorylcholine
• tricyclodecane-9-yl-xanthogenate
• Protein Kinase C
• Type C Phospholipases
• Phospholipase D
• Phosphatidylinositol Diacylglycerol-Lyase

Topics

• Bridged-Ring Compounds (pharmacology)
• Diglycerides (biosynthesis)
• Humans
• Immunoglobulin G (pharmacology)
• Norbornanes
• Pemphigus (immunology)
• Phosphatidylinositol Diacylglycerol-Lyase
• Phospholipase D (physiology)
• Phosphorylcholine (metabolism)
• Protein Kinase C (physiology)
• Signal Transduction
• Thiocarbamates
• Thiones (pharmacology)
• Tumor Cells, Cultured
• Type C Phospholipases (physiology)