title: Protease nexin-2/amyloid beta-protein precursor in blood is a platelet-specific protein.
abstract: The protease inhibitor, protease nexin-2 (PN-2), is the secreted form of the amyloid beta-protein precursor (APP) which contains the Kunitz protease inhibitor domain. PN-2/APP is an abundant platelet alpha-granule protein which is secreted upon platelet activation. PN-2/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 less than or equal to 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine 92717.
authors.forename: W E
authors.initials: WE
authors.lastname: Van Nostrand
authors.forename: A H
authors.initials: AH
authors.lastname: Schmaier
authors.forename: J S
authors.initials: JS
authors.lastname: Farrow
authors.forename: D B
authors.initials: DB
authors.lastname: Cines
authors.forename: D D
authors.initials: DD
authors.lastname: Cunningham
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D016564:Amyloid beta-Protein Precursor; D001792:Blood Platelets / Q000502:physiology*; D002352:Carrier Proteins / Q000097:blood* / Q000302:isolation & purification; D004730:Endothelium, Vascular / Q000737:chemistry; D006098:Granulocytes / Q000737:chemistry; D006801:Humans; D015151:Immunoblotting; D009000:Monocytes / Q000737:chemistry; D015849:Plasminogen Inactivators / Q000097:blood*; D058255:Protease Nexins; D011498:Protein Precursors / Q000737:chemistry*; D011956:Receptors, Cell Surface; D012016:Reference Values
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D015849:Plasminogen Inactivators; D058255:Protease Nexins; D011498:Protein Precursors; D011956:Receptors, Cell Surface