AbstractAs β1 and β2 integrins were previously found to mediate adhesion during IL‐4‐induced foreign body giant cell (FBGC) formation, we pursued the identities of the α integrin partners of these adhesion receptors using our in vitro system of human monocyte‐derived macrophage fusion. Immunoprecipitation with β1 and immunoblotting reveal the presence of α5 and αV, as well as α2 and α3. αM and αX immunoprecipitate with β2 but not with β1. Immunocytochemistry coupled with confocal microscopy indicates that α5 and αX are poorly expressed on day 0. However, following the induction of fusion by IL‐4 on day 3, they are each readily detectable in fusing macrophages/FBGC on day 7. In contrast, αM and αV are present throughout the culture period, with very strong αM expression on day 7. We also demonstrate expression and colocalization of α3, α5, or αV with β1 on fusing macrophages/FBGC at this time point as well as strong colocalization of αM and αX with β2 in FBGC and at fusion interfaces. Therefore, IL‐4‐induced FBGC are characterized by the expression of αMβ2, αXβ2, α5β1, αVβ1, α2β1, and α3β1, which indicates potential interactions with fragments of complement C3, fibrin(ogen), fibronectin, Factor X, and vitronectin, and possibly with certain collagens, laminin, and thrombospondin at sites of biomaterial implantation. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007