Modulatory effect of the RGD and PHSRN amino acid sequences of fibronectin on macrophage adhesion and multinucleated giant cell formation

b1-Integrin plays a key role in macrophage adhesion to all substrates, whereas b3-integrins play an important but lesser role. Macrophages adhere to all substrates with rel. subtle differences between adhesion mediated by RGD, PHSRN, PRRARV, or combinations thereof. Macrophage adhesion to the heparin-binding PRRARV domain is mediated primarily by direct interaction with integrins, rather than by cell-surface heparin sulfate proteoglycan. The RGD sequence alone does not provide an adequate substrate for macrophage fusion to form FBGCs (foreign body giant cells). By contrast, the PHSRN synergistic site does provide a substrate that is permissive of FBGC formation. The PHSRN synergistic site together with the RGD site provides a substrate for FBGC formation that is comparable with that on pos. control material mediated by adsorbed proteins. This response is highly dependent upon the rel. orientation of the RGD and the PHSRN domains. The heparin-binding sequence PRRARV seems to play no role in supporting FBGC formation. There is synergy between the RGD and the PHSRN domains in supporting macrophage fusion to form FBGCs, but not adhesion. [on SciFinder (R)]