Hr. Lijnen et al., PLASMINOGEN PLASMIN AND MATRIX METALLOPROTEINASE SYSTEM FUNCTION IN MICE WITH TARGETED INACTIVATION OF STROMELYSIN-3 (MMP-11)/, FIBRINOLYSIS & PROTEOLYSIS, 12(3), 1998, pp. 155-164
Citations number
40
Categorie Soggetti
Hematology,Biology,"Medicine, Research & Experimental
The role of stromelysin-3 (MMP-11) in plasminogen/plasmin and matrix m
etalloproteinase system function was investigated with the use of MMP-
11-deficient (MMP-11(-/-)) mice. Haemostasis analysis of blood and pla
sma obtained from wild-type (MMP-11(+/+)) or MMP-11(-/-) mice did not
reveal significant differences. Urinary u-PA antigen (380-600 ng/ml) a
nd activity levels (62-65 IU/ml) were comparable. Vascular tissue-type
(t-PA) or urokinase-type (u-PA) plasminogen activator activities were
not significantly different in aorta extracts of MMP-11(+/+) or MMP-1
1(-/-) mice. In vivo thioglycollate-stimulated macrophages of both gen
otypes expressed comparable u-PA-mediated plasminogen activating poten
tial and fibrin or extracellular matrix degrading capacity. Organ sect
ions did not show significant fibrin deposition in the liver of MMP-11
(+/+) or MMP-11(-/-) mice. In purified systems, a murine MMP-11 fragme
nt containing the catalytic domain degraded fibrinogen, mainly by clea
vage of the A alpha-chain, but did not significantly lyse fibrin. Acti
ve and latent MMP-2 (gelatinase A) and MMP-9 (gelatinase B) levels wer
e comparable in aorta extracts of MMP-11(+/+) and MMP-11(-/-) mice. Ce
ll culture experiments confirmed comparable ratios of active versus la
tent MMP-2 and MMP-9 in fibroblasts, smooth muscle cells and macrophag
es derived from both genotypes. These data suggest that fibrinolytic a
ctivity mediated via the plasminogen/plasmin system does not require M
MP-11, and that MMP-11 does not play a major physiological role in the
expression or activation of gelatinases.