Alteration of the chemotactic response of human skin fibroblasts to PDGF by growth factors.

Platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant for fibroblastic cells. In the early stage of wound healing. PDGF is released from aggregated platelets and it is believed that its chemotactic activity may play a key role in the influx of connective tissue cells into wound sites. Using the Boyden chamber assay, we investigated factors that alter the migratory response of human skin fibroblasts to PDGF. The response was related to the growth state of cells; that is, growing cells at low cell density exhibited a greater migratory response to PDGF than density-arrested quiescent cells. The level of random migration was also elevated in growing cells, compared to quiescent cells. The chemotactic response after 3-h exposure to serum was markedly decreased (> 50%). Three-hour preincubation of the cells with transforming growth factor-beta (TGF-beta) or with epidermal growth factor reduced the migratory response to approximately half that in the nonstimulated control. In contrast, cells treated with TGF-beta or basic fibroblast growth factor for 24 h exhibited a two- to threefold greater chemotactic response to PDGF than control cells. This stimulatory effect of TGF-beta on the fibroblast migration induced by PDGF suggests that TGF-beta acts synergistically with PDGF on the influx of connective tissue cells into human wound sites and may explain the potent wound healing activity of TGF-beta in vivo.