Insulin-like growth factor-binding protein-3 binds fibrinogen and fibrin

Following tissue injury, a fibrin network formed at the wound site serves a s a scaffold supporting the early migration of stromal cells needed for wou nd hearing. Growth factors such as insulin-like growth factor-I (IGF-I) con centrate in wounds to stimulate stromal cell function and proliferation. Th e ability of IGF-binding proteins (IGFBPs) such as IGFBP-3 to reduce the ra te of IGF-I clearance from wounds suggests that IGFBP-3 might bind directly to fibrinogen/fibrin. Studies presented here show that IGFBP-3 does indeed bind to fibrinogen and fibrin immobilized on immunocapture plates, with K- d values = 0.67 and 0.70 nM, respectively, and competitive binding studies suggest that the IGFBP-3 heparin binding domain may participate in this bin ding. IGF-I does not compete for IGFBP-3 binding; instead, IGF-I binds immo bilized IGFBP-3 fibrinogen and IGFBP-3 fibrin complexes with affinity simil ar to that of IGF-I for the type I IGF receptor. In the presence of plasmin ogen, most IGFBP-3 binds directly to fibrinogen, although 35-40% of the IGF BP-3 binds to fibrinogen-bound plasminogen, IGFBP-3 also binds specifically to native fibrin clots, and addition of exogenous IGFBP-3 increases IGF-I binding. These studies suggest that IGF-I can concentrate at wound sites by binding to fibrin-immobilized IGFBP-3, and that the lower IGF affinity of fibrin-bound IGFBP-3 allows IGF-I release to type I IGF receptors of stroma l cells migrating into the fibrin clot.