Purified monocyte-derived angiogenic substance (angiotropin) induces controlled angiogenesis associated with regulated tissue proliferation in rabbit skin.

Angiotropin is a differentiation factor for microvascular endothelial cells isolated from serum-free cultures of lectin-activated, porcine monocytes. We used an ear lobe model in rabbits, single intradermal injection of angiotropin to induce phenotypical changes of the endothelial cells in capillaries and postcapillary venules, vascular engorgement, and subsequent angiogenesis in dose-dependent manner. The vascular changes are associated with epidermal and stromal cell proliferation. Angiogenesis and tissue proliferation occur in the absence of tissue necrosis and do not lead to scar formation. Angiotropin-induced angiogenesis is not inhibited by local dexamethasone although it involves a defined turnover of inflammatory cells. Proliferation is transient and regressive events follow. The overall tissue reaction resembles changes found in the undamaged skin margin of a primary healing wound during the inflammatory/proliferative phase. From these observations we conclude that angiotropin is an important secretory product of activated peripheral macrophages that triggers inflammatory and proliferative reactions in wound healing by activating microvascular endothelial cells.