Cell surface-bound urokinase-type plasminogen activator facilitates infiltration of freshly isolated granulocytes into fibrin matrix.
Human cell lines of myelo/monocytic origin express the cellular receptor for urokinase-type plasminogen activator (uPA-R). The receptor localizes urokinase-type plasminogen activator (uPA) to the surface of the cell, where it can convert plasminogen to the active serine proteinase plasmin. Plasmin may subsequently account for proteolysis of pericellular proteins. We demonstrated the expression of the uPA-R by freshly isolated neutrophilic granulocytes by using a specific mAb. In freshly isolated granulocytes we detected only a weak occupation of the uPA-R; further uPA binding by granulocytes was saturable and proceeded in a dose-dependent manner. Receptor-bound uPA retained its enzymatic activity. Saturation of isolated granulocytes with exogenous uPA enhanced cellular infiltration into a fibrin matrix in vitro. uPA-dependent infiltration was inhibited by an anti-catalytic monoclonal anti-uPA antibody. The findings show that circulating neutrophilic granulocytes express the cell surface uPA-R and suggest that surface-binding of uPA may facilitate the infiltration of granulocytes into a fibrin clot, a process that might add to thrombolysis in vivo.
Herijgers
N
N
Department of Immunohematology and Bloodbank, University Hospital, Leiden, Netherlands.
Vettel
U
U
Schaefer
B
B
Spring
H
H
Todd
R F
RF
Kramer
M D
MD
D002465:Cell Movement / Q000187:drug effects*; D002469:Cell Separation / Q000592:standards; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis*; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000502:physiology; D005337:Fibrin; D005434:Flow Cytometry / Q000592:standards; D005782:Gels; D006098:Granulocytes / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000494:pharmacology* / Q000592:standards; D010958:Plasminogen / Q000187:drug effects; D010960:Plasminogen Activators / Q000502:physiology; D011786:Quality Control; D011956:Receptors, Cell Surface / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology* / Q000592:standards
D003470:Culture Media; D016207:Cytokines; D005782:Gels; D008565:Membrane Proteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D005337:Fibrin; D010958:Plasminogen; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator