The function of multiple extracellular matrix receptors in mediating cell adhesion to extracellular matrix: preparation of monoclonal antibodies to the fibronectin receptor that specifically inhibit cell adhesion to fibronectin and react with platelet glycoproteins Ic-IIa.

TLDR

Members of the ECMR family possess distinct alpha subunits and a common ~140 kD beta subunit, and their differential expression in platelets, lymphocytes, and various tissue cells suggests a role in vascular emigration and tissue localization. The authors used monoclonal antibodies against FNR and ECMR II to demonstrate that blocking both receptors is required to completely inhibit cell adhesion to cell‑derived extracellular matrix. The study identified monoclonal antibodies that block adhesion to collagen and fibronectin by targeting ECMRs II, VI, and I, showed that ECMR VI is the fibronectin receptor (FNR), and found that antibodies to FNR inhibit lymphocyte, fibroblast, and platelet adhesion to fibronectin; tissue staining localized ECMRs I and II to basal epidermis and FNR to dermis and epidermis, indicating that multiple ECMRs cooperate to mediate adhesion to complex extracellular matrix and may direct tissue.

Abstract

We have identified monoclonal antibodies that inhibit human cell adhesion to collagen (P1H5), fibronectin (P1F8 or P1D6), and collagen and fibronectin (P1B5) that react with a family of structurally similar glycoproteins referred to as extracellular matrix receptors (ECMRs) II, VI, and I, respectively. Each member of this family contains a unique alpha subunit, recognized by the antibodies, and a common beta subunit, each of approximately 140 kD. We show here that ECMR VI is identical to the fibronectin receptor (FNR), very late antigen (VLA) 5, and platelet glycoproteins Ic-IIa and shall be referred to as FNR. Monoclonal antibodies to FNR inhibit lymphocyte, fibroblast, and platelet adhesion to fibronectin-coated surfaces. ECMRs I, II, and FNR were differentially expressed in platelets, resting or activated lymphocytes, and myeloid, epithelial, endothelial, and fibroblast cell populations, suggesting a functional role for the receptors in vascular emigration and selective tissue localization. Tissue staining of human fetal skin localized ECMRs I and II to the basal epidermis primarily, while monoclonal antibodies to the FNR stained both the dermis and epidermis. Experiments carried out to investigate the functional roles of these receptors in mediating cell adhesion to complex extracellular matrix (ECM) produced by cells in culture revealed that complete inhibition of cell adhesion to ECM required antibodies to both the FNR and ECMR II, the collagen adhesion receptor. These results show that multiple ECMRs function in combination to mediate cell adhesion to complex EMC templates and predicts that variation in ECM composition and ECMR expression may direct cell localization to specific tissue domains.