Microglia isolated from rat brain secrete a urokinase-type plasminogen activator.
In a previous study, we found particular proteases which degrade myelin basic protein (MBP) in a conditioned medium of cultured rat brain microglia. The MBP degrading activity in microglial-conditioned medium (Mic-CM) increased markedly in the presence of plasminogen. By Sephadex G-150 column chromatography, plasminogen-dependent MBP degrading activity was eluted at the position of about 47 kDa and 28 kDa. Furthermore slight plasminogen-dependent protease activity in the presence of fibrin (tissue plasminogen activator activity) was detected at a molecular weight of about 68 kDa. The two molecular forms (47 kDa and 28 kDa) of plasminogen-dependent protease were demonstrated by casein-zymography, and it was suggested that they were urokinase type-plasminogen activators (uPA). This suggestion was confirmed by immunoblotting using anti-uPA antiserum. The unique 28 kDa type was considered to be produced from the 47 kDa form by limited proteolysis. Secretion of PA from microglia was demonstrated by cell zymography. In contrast, significant secretion of plasminogen activator inhibitor could not be detected in the Mic-CM. In addition, lipopolysaccharide significantly decreased the secretion of PA from microglia, while interleukin-1 and basic fibroblast growth factor enhanced the secretion.
Nakajima
K
K
Department of Neurochemistry, National Institute of Neuroscience, Tokyo, Japan.
Tsuzaki
N
N
Shimojo
M
M
Hamanoue
M
M
Kohsaka
S
S
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D003238:Connective Tissue / Q000378:metabolism*; D003239:Connective Tissue Cells; D004591:Electrophoresis, Polyacrylamide Gel; D008970:Molecular Weight; D004676:Myelin Basic Protein / Q000378:metabolism; D051381:Rats; D013053:Spectrophotometry; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000378:metabolism* / Q000502:physiology
D004676:Myelin Basic Protein; D014568:Urokinase-Type Plasminogen Activator