Relationships between phosphatidylcholine-specific phospholipase C and integrins in cell-substratum adhesion and apoptosis in vascular endothelial cells.
In order to understand the mechanism by which VEC control cell-substratum adhesion and apoptosis, we investigated relationships between PC-PLC and the integrins that are normally expressed in VEC. We found that promotion of cell-substratum adhesion by suppression of PC-PLC was almost completely blocked by a monoclonal antibody (mAb) against integrin beta1, and was partially blocked by a mAb against intergrin beta3. The production of diacylglycerol (DAG) which was inhibited by suppression of PC-PLC activity, was increased by mAbs against intergrin beta1 and beta3. When the mAb against integrin beta4 was added to the seeding medium, cell-substratum adhesion and spreading of cells were triggered, but the activity of PC-PLC was unaffected by this mAb. Furthermore, when both the mAb against integrin beta4 and a specific inhibitor (D609) of PC-PLC were present in the seeding medium, cell-substratum adhesion and spreading were promoted to a greater extent than when either of these agents was present alone. These data suggest that integrins beta1 and beta3 might regulate cell-substratum adhesion and apoptosis via a PC-PLC-dependent pathway, while integrin beta4 might regulate these phenomena via PC-PLC-independent pathway. These findings provide the first evidence of relationships between PC-PLC and integrins in cell-substratum adhesion and apoptosis.
Miao
J Y
JY
Sugashima Marine Biological Laboratory, School of Science, Nagoya University, Toba, Mie, Japan.
Araki
S
S
Hayashi
H
H
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D017209:Apoptosis; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology; D039661:Integrin beta3; D039663:Integrin beta4; D016023:Integrins / Q000502:physiology*; D009636:Norbornanes; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010740:Phospholipases; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000502:physiology; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology*; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001952:Bridged-Ring Compounds; D019012:Integrin beta1; D039661:Integrin beta3; D039663:Integrin beta4; D016023:Integrins; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors; D010980:Platelet Membrane Glycoproteins; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D010740:Phospholipases; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase