Expression of the activation marker urokinase plasminogen-activator receptor in cultured human central nervous system...

The ability of microglia to migrate through central nervous system (CNS) tissue requires proteolytic degradation of components of the extracellular matrix. Urokinase plasminogen activator (uPA), when bound to its cell surface receptor (uPAR), is an active cell surface protease. uPAR expression has been associated with cell activation. Cultured human microglia express surface uPAR. uPAR expression was found to be associated predominately with spindle- or bipolarshaped microglia. The addition of lipopolysaccharide (LPS) to microglial cultures enhanced the proportion of uPAR expression and shifted cell morphology to the elongated spindle or bipolar shape. When microglia were examined immediately ex vivo, uPAR surface expression could not be detected. Similarly, uPAR transcripts detected by reverse transcription-polymerase chain reaction techniques were found in cultured, but not ex vivo, microglia. Microglia isolated from a patient with multiple sclerosis (MS) displayed a large amount of uPAR+ cells. These cells were predominantly spindle or bipolar in nature. These findings suggest that uPAR surface expression is associated with microglial activation. Surface expression of uPAR and associated cell surface protease activity may provide a mechanism for microglial migration and may be important in the pathophysiology of MS.