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Modulation of Fibrinolysis by Thrombospondin a
Author(s) -
MOSHER DEANE F.,
MISENHEIMER TINA M.,
STENFLO JOHAN,
HOGG PHILIP J.
Publication year - 1992
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1992.tb51598.x
Subject(s) - library science , general hospital , chemistry , medicine , computer science , pediatrics
Thrombospondin is a large, trimeric glycoprotein secreted by activated platelets and growing cells. Thrombospondin copolymerizes with fibrin during blood coagulation and deposits in extracellular matrix. We found that thrombospondin is a slow (rate constant approximately 6.3 x 10(3) M-1 sec-1), tight-binding (Kd < 10(-9) M) inhibitor of plasmin as determined by loss of amidolytic activity, loss of ability to degrade fibrinogen, and decreased lysis zones in fibrin plate assays (Biochemistry 31: 265-269, 1992). Thrombospondin also slowly inhibits urokinase plasminogen activator. The lysis zone when urokinase is put on fibrin plates made from whole plasma is less if thrombospondin is present. The stoichiometry of inhibition is approximately one mole plasmin:one mole thrombospondin trimer, a somewhat surprising result considering the trimeric nature of thrombospondin. These results indicate that thrombospondin is an important regulator of fibrinolysis and degradation of extracellular matrix, particularly when these processes are initiated by urokinase and even when other inhibitors of fibrinolysis are present.