Clearance of IGFs and insulin from wounds: effect of IGF-binding protein interactions

We have examined the role binding proteins have in regulating the clearance of exogenous growth factors from wounds. Hunt-Schilling chambers were subc utaneously implanted in rats, and the clearance of insulin-like growth fact or (IGF) I from the chamber wound fluid was compared with IGF-II, LR3-IGF-I , which binds poorly to ICE-binding proteins (IGFBP), or insulin. Eliminati on rate constants of the slow phase of the decay curves did not differ betw een IGF-I and IGF-II. However, LR3-IGF-I and insulin were cleared more rapi dly from wound fluid than IGF-I so that the half-lives for IGF-I, IGF-II, L R3-IGF-I, and insulin were 872, 861., 563, and 324 min, respectively. In wo und fluid, minimal degradation of the IGFs occurred, whereas insulin was de graded considerably. The increased clearance of LR3-IGF-I and insulin equat ed with a reduced association with wound fluid IGFBPs, and increased amount s of radioactivity of these peptides were detected in the circulation and u rine. These results show that this model of wound repair may be of use in e xamining the kinetics of growth factors and other bioactive molecules in ex travascular spaces and support the hypothesis that IGFBPs can be significan t regulators of IGF bioavailability in vivo.