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 beta 1, and was partially blocked by a mAb against intergrin beta 3. The production of diacylglycerol (DAG) which was inhibited by suppression of PC-PLC activity, was increased by mAbs against intergrin beta 1 and beta 3. When the mAb against integrin beta 4 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 beta 4 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 beta 1 and beta 3 might regulate cell-substratum adhesion and apoptosis via a PC-PLC-dependent pathway, while integrin beta 4 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.