Leukotriene B4 induces in vitro fibroblast chemotaxis

In vitro fibroblast chemotaxis was studied in the presence of synthetic leukotriene B4 (LTB4) and of supernatants from ionophore-stimulated lymphocytes, monocytes, and basophils (LMB-S). LTB4 and LMB-S induced a dose-related, directed migration of human and rat embryonic fibroblasts. By checkerboard analysis, this response was chemotactic and not chemokinetic. Optimal migration toward LTB4 occurred at 10(-8) M concentrations, while higher concentrations were inhibitory. The LMB-S contained two types of fibroblast chemotactic factors, one that corresponded to LTB4 and one additional, heat labile, non-dialyzable substance of greater than 10 kilodaltons. LTB4 and LMB-S were inactive against transformed human connective tissue cells (HT 1080, McCoy) while these cells moved well in response to conditioned medium derived from confluent fibroblast monolayer cultures. These results suggest that LTB4 is a specific chemoattractant for fibroblasts and that it acts in concert with other chemotactic factors derived from inflammatory leukocytes to regulate the influx of fibroblasts to tissue sites.