A Synthetic Peptide, FN-C/H-V, from the C-Terminal Heparin-Binding Domain of Fibronectin Promotes Adhesion of PMA Stimulated U937 Cells

Abstract

Hematopoietic cells differentially bind to the C-terminal heparin-binding domain of fibronectin depending on the activation state of integrin α4β1. In this study, we have identified a synthetic peptide derived from the C-terminal heparin-binding domain of fibronectin that promotes adhesion of PMA-treated U937 cells (a monocytic cell line) in a dose-dependent manner. A peptide (FN-C/H-V; residues Gln1892to Gly1910) was active to inhibit adhesion of PMA-treated U937 cells to the 29-kDa fragment comprising the C-terminal heparin-binding domain of fibronectin. A peptide with scrambled version of FN-C/H-V lost the inhibitory activity on the adhesion. Furthermore, the IgG-conjugated FN-C/H-V promoted the adhesion of PMA-treated U937 cells to an extent comparable to that of the 29-kDa fragment. The adhesion of PMA-treated U937 cells on IgG-conjugated FN-C/H-V was inhibited both by anti-α4β1antibody and by glycosaminoglycans including chondroitin sulfate and heparan sulfate. The other peptide, FN-C/H-II, was also a weak adhesion-promoting domain. These results suggest that the amino acid sequence defined by peptide FN-C/H-V contributes to the main adhesion-promoting activity of the 29-kDa fragment of fibronectin to stimulated U937 cells. The regulation of interactions of α4β1integrin and glycosaminoglycans with ligands in fibronectin may have important implications for the migration and function of U937 cells.