Vascular and cellular proteolytic activity in mice with α2-antiplasmin gene inactivation

Objective: To study the role of α₂-antiplasmin (α₂-AP), the main physiological plasmin inhibitor, in controlling vascular and cellular proteolytic activity.

Materials: Arteries, organs and cell cultures derived from α₂-AP-deficient (α₂-AP^–/–) mice or from their wild-type littermates (α₂-AP^+/+).

Results: In serum-free conditioned medium of α₂-AP^+/+or α₂-AP^–/–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 proMMP-9 (gelatinase B) upon addition of plasmin(ogen) to serum-free conditioned medium of fibroblasts was consistently detectable with α₂-AP^–/–but not with α₂-AP^+/+cells. In aorta and femoral arterial extracts of α₂-AP^+/+or α₂-AP^–/–mice, t-PA and u-PA activity levels were comparable, and fibrin zymography with cryosections did not reveal significant differences in fibrinolytic activity. In liver or kidney extracts of α₂-AP^+/+or α₂-AP^–/–mice, t-PA, u-PA, PAI-1 and plasminogen antigen levels were comparable; t-PA or u-PA activity was not detected in liver extracts and was present at comparable levels in kidney extracts.

Activation of plasminogen to plasmin in solution by cell-associated plasminogen activator, and activation of cell-bound plasminogen by tcu-PA was comparable for fibroblasts of both genotypes.

Conclusions: α₂-AP does not play a crucial role in controlling vascular or cellular proteolytic activity in mice.