Fibroblast production of extracellular matrix is crucial not only for normal tissue development and maintenance of tissue structure but also for the repair and remodeling processes after injury. Thromboxane A2 (TXA2) is a potent mediator in inflammatory processes. The aim of this study was to investigate the effect of TXA2 on chemotaxis of human fetal lung (HFL-1) fibroblasts induced by human plasma fibronectin or platelet-derived growth factor BB (PDGF-BB). By using the blindwell chamber technique, the TXA2 agonist U-46619 alone had no chemotactic activity. However, U-46619 (200 nmol/L) stimulated HFL-1 fibroblast chemotaxis to human plasma fibronectin (20 μg/mL; 161.8% ± 13.4%; P <.005) and to PDGF-BB (10 ng/mL; 188.5% ± 7.0%; P <.005). Checkerboard analysis of human plasma fibronectin-directed migration confirmed that the TXA2 agonist increased both chemotaxis and chemokinesis. The stimulatory effect of the TXA2 agonist was concentration dependent and increased with time. Another agent known for stimulating the protein kinase C pathway, phorbol 12-myristate 13-acetate (10−8 mol/L), had a similar effect, stimulating chemotaxis to fibronectin (146.2% ± 8.6%). The stimulatory effect of the TXA2 agonist on HFL-1 fibroblast chemotaxis was inhibited by the synthetic thromboxane receptor antagonist SQ29, 548 (10−5 mol/L) and the protein kinase C inhibitor calphostin (10−7 mol/L). In summary, TXA2 appears to stimulate fibroblast chemotaxis to fibronectin and PDGF, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of wound healing and the development of fibrotic disorders.
ASJC Scopus subject areas
- Pathology and Forensic Medicine