Protease nexin-2/amyloid β-protein precursor in blood is a platelet-specific protein

The protease inhibitor, protease nexin-2 (PN-2), is the secreted form of the amyloid β-protein precursor (APP) which contains the Kunitz protease inhibitor domain. PN2/APP is an abundant platelet α-granule protein which is secreted upon platelet activation. PN2/APP mRNA is present in cultured endothelial cells and the protein has been detected in plasma. In the present studies we quantitated PN-2/APP in platelets, plasma and several different cell types of the vasculature to identify the repository of the protein in the circulatory system. We report that PN-2/APP is predominantly a platelet protein in the vascular compartment. Lysates of unstimulated umbilical vein endothelial cells, granulocytes or monocytes contained little PN-2/APP based on sensitive functional protease binding and immunoblotting assays. Quantitative immunoblotting studies demonstrated that normal citrated-plasma contains ≤ 60 pM PN-2/APP. In contrast, platelets can contribute up to 30 nM PN-2/APP, indicating that they are the major source of the protein in blood.