Expression of Functional α4β1 Integrin by Human Dermal Fibroblasts

Fibroblasts interact with the extracellular matrix through cell-surface receptors belonging to the integrin family. In this report, we present evidence that cultured normal human fibroblasts express the integrin α4β1 and that this receptor facilitates fibroblast attachment to fibronectin. Fluorescence-activated cell sorter analysis and immunoprecipitation with monoclonal antibodies demonstrated that normal dermal fibroblasts express the α4-subunit on the cell surface, primarily in association with the β1-subunit. Cell-attachment assays demonstrated that normal human fibroblasts can attach to the 40-kDa fibronectin fragment containing the type III connecting segment domain recognized by α4β1. Adhesion to this fragment was inhibited by anti-α4 antibody. Furthermore, our results indicate that α4β1 collaborates with another fibronectin receptor, α5β1, during fibroblast attachment to full-length fibronectin. The region of fibronectin recognized by α5β1 contains the amino acid sequence arg-gly-asp (RGD). A short synthetic RGD peptide, or the 120-kDa fibronectin fragment containing the RGD sequence, only partially inhibited attachment to full-length fibronectin, suggesting that fibroblasts utilize more than the RGD recognition sequence for binding to fibronectin. Accordingly, RGD peptide combined with anti-α4 antibody produced more potent inhibition of cell attachment than either reagent alone. These observations show for the first time that functional α4β1 fibronectin receptor is not restricted to lymphoid cells and transformed cells