Interleukin-4 Mediated Foreign Body Giant Cell Formation and Cytoskeletal Rearrangement on Poly(etherurethane Urea) In Vivo and In Vitro

Abstract

Interleukin-4 (IL-4) mediated foreign body giant cell (FBGC) formation on poly(etherurethane urea) (PEUU) in vivo was studied using the subcutaneous cage system in mice. Purified goat anti-mouse IL-4 neutralizing antibody (IL4Ab), normal goat nonspecific control IgG (gtIgG), recombinant murine IL-4 (muIL4), or PBS was injected into the implanted cages containing PEUU every two days for 7 days. The injection of IL4Ab significantly decreased the FBGC density on PEUU cage-implanted in mice, when compared with the nonspecific gtlgG or PBS injection controls. Conversely, the FBGC density was significantly increased by the injection of muIL4 when compared with nonspecific gtIgG and PBS injection controls. Confocal scanning laser microscopy (CSLM) was employed to visualize the spatial arrangement of the filamentous actin cytoskeleton of adherent macrophages and IL-4-induced FBGCs in vitro. Whereas the material surface-associated punctate actin structures occurred across the entire ventral cell surface in monocytes/macrophages cultured on PEUU, the structures became restricted to the periphery of the ventral cell surface upon addition of IL-4 as fused macrophages acquired FBGC phenotype. Our data suggest that IL-4 participates in FBGC formation on biomaterials in vivo and in vitro and that dramatic reorganization of the cytoskeleton occurs during FBGC formation.