The proliferative response in vitro of vascular endothelial and smooth muscle cells exposed to wound fluids and macrophages

The ability of wound‐derived macrophages and of fluids obtained from wounds to stimulate the proliferation of vascular endothelial cells and vascular smooth muscle cells in vitro has been investigated. Sparse cultures of endothelial and smooth muscle cells maintained in the presence of optimal concentrations of serum and wound fluid showed a 25‐fold increase and a 10‐fold increase, respectively, in final cell density when compared to cultures maintained in the presence of serum alone. The response of both endothelial and smooth muscle cells to the wound fluid was dependent on the serum or plasma‐serum concentrations in which they were maintained. The ability of the wound fluid to stimulate endothelial cell proliferation was compared to that of fibroblast growth factor (FGF), which has already been shown to be a potent mitogen for endothelial cells in vitro. The growth response of endothelial cell cultures, when exposed to either 2% wound fluid or 100 ng/ml of FGF, was found to be similar, and the normal cell morphology was maintained. To examine the possibility that the growth stimulating activity present in the wound fluid originated from macrophages, endothelial cells or smooth muscle cells were co‐cultured with macrophages obtained from the wound fluid. A significant stimulation of both endothelial and smooth muscle cells was observed with 2 × 106 macrophages, which would suggest that macrophages may be the source of the mitogenic activity of the wound fluid in vivo.