ENDOTHELIAL-CELL-STIMULATING ANGIOGENESIS FACTOR (ESAF) ACTIVATES PROGELATINASE-A (72 KDA TYPE-IV COLLAGENASE), PROSTROMELYSIN-1 AND PROCOLLAGENASE AND REACTIVATES THEIR COMPLEXES WITH TISSUE INHIBITORS OF METALLOPROTEINASES - A ROLE FOR ESAF IN NONINFLAMMATORY ANGIOGENESIS

Endothelial-cell-stimulating angiogenesis factor (ESAF) has been shown to activate procollagenase and reactivate complexes of collagenase an d gelatinase A with tissue inhibitor of metalloproteinase (TIMP)-1. In the present paper we show a purification protocol for bovine pineal E SAF and that purified ESAF activates progelatinase A and prostromelysi n-1. Unlike the activation of procollagenase by plasmin/plasminogen ac tivator, which requires the presence of stromelysin for full activatio n, ESAF is able to activate fully all three proenzymes. Purified ESAF is also shown to reactivate the complexes of gelatinase A, collagenase and stromelysin-1 with TIMP-2. Once separated, both enzyme and inhibi tor are active; however, ESAF binds to the enzyme in a manner preventi ng it from further inhibition by TIMP. ESAF is the only physiological molecule able to reactivate the TIMP/enzyme complex.