Reciprocal regulation of urokinase receptor (CD87)-mediated cell adhesion by plasminogen activator inhibitor-1 and protease nexin-1.
Protease nexin-1 (PN-1) and plasminogen activator inhibitor-1 (PAI-1) are serine protease inhibitors that bind to the extracellular matrix protein vitronectin (VN) with high affinity. PAI-1 is known to inhibit cell adhesion and migration by binding to VN and inhibiting the interaction with integrins or the urokinase receptor (uPAR). Unexpectedly, PN-1 was found to increase the association between VN and uPAR in the presence of enzymatically active uPA. Through this mechanism PN-1 also stimulated uPAR-dependent cell adhesion to immobilized VN. In contrast to PAI-1, PN-1 did not influence VN binding to integrins or integrin-mediated cell adhesion. Upon adhesion of monocytes to VN there was an accumulation of uPAR and PN-1 at the interface between the cell and the matrix, whereas on fibronectin (FN) both components were distributed evenly over the whole cell as visualized by confocal microscopy. Immunohistochemistry of atherosclerotic vessels indicated that PN-1 was found associated with smooth muscle cells, macrophages and platelets. In some regions of the diseased vessels PN-1 was in close proximity to VN and uPAR, but no PN-1 was present in normal vessels. These results indicate a novel function of PN-1 linked to complex formation with uPA that leads to the regulation of VN-dependent adhesion of leukocytes.
Kanse
Sandip M
SM
Institute for Biochemistry, Justus-Liebig-University, 35392 Giessen, Germany. sandip.kanse@biochemie.med.uni-giessen.de
Chavakis
Triantafyllos
T
Al-Fakhri
Nadia
N
Hersemeyer
Karin
K
Monard
Denis
D
Preissner
Klaus T
KT
D016564:Amyloid beta-Protein Precursor; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D058258:Serpin E2; D019096:Vitronectin / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D016023:Integrins; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C545486:SERPINE2 protein, human; D058258:Serpin E2; D019096:Vitronectin