Vascular and cellular proteolytic activity in mice with alpha(2)-antiplasmin gene inactivation

Objective: To study the role of alpha(2)-antiplasmin (alpha(2)-AP), the mai n physiological plasmin inhibitor, in controlling vascular and cellular pro teolytic activity. Materials: Arteries, organs and cell cultures derived from alpha(2)-AP-defi cient (alpha(2)-AP(-/-)) mice or from their wild-type littermates (alpha(2) -AP(+/+)). Results: In serum-free conditioned medium of alpha(2)-AP(+/+) or alpha(2)-A P(-/-) skin fibroblasts, the time course (0-72 h) of PAI-1 antigen and of t -PA or u-PA antigen and activity production was similar. Activation of proM MP-9 (gelatinase B) upon addition of plasmin(ogen) to serum-free conditione d medium of fibroblasts was consistently detectable with alpha(2)-AP(-/-) b ut not with alpha(2)-AP(+/+) cells. In aorta and femoral arterial extracts of alpha(2)-AP(+/+) or alpha(2)-AP(-/-) mice, t-PA and u-PA activity levels were comparable, and fibrin zymography with cryosections did not reveal si gnificant differences in fibrinolytic activity. In liver or kidney extracts of alpha(2)-AP(+/+) or alpha(2)-AP(-/-) mice, t-PA, u-PA, PAI-1 and plasmi nogen antigen levels were comparable; t-PA or u-PA activity was not detecte d in liver extracts and was present at comparable levels in kidney extracts . Activation of plasminogen to plasmin in solution by cell-associated plasm inogen activator, and activation of cell-bound plasminogen by tcu-PA was co mparable for fibroblasts of both genotypes. Conclusions: alpha(2)-AP does not play a crucial role in controlling vascul ar or cellular proteolytic activity in mice. (C) 2000 Harcourt Publishers L td.