THE ROLE OF GM-CSF IN MACROPHAGE POLARISATION IN RESPONSE TO TROPOELASTIN-COATED POLYETHYLENE IMPLANTS IN VIVO

Abstract

Our previous studies have shown that the incorporation of tropoelastin (TE) improves the biocompatibility of silk fibroin and low density polyethylene (PE). With the coating or blending of tropoelastin, both biomaterials underwent a favourable foreign body inflammatory response. Macrophage is a key cell in the biomaterial-induced inflammation and can be polarized into two main phenotypes (M1/M2) capable of inducing either pro-inflammatory or anti-inflammatory cytokine profiles during host responses. The objective of the present study was to investigate the possible underling mechanism of the improved biocompatibility with tropoelastin coating in terms of macrophage response. The macrophage infiltration and polarization was evaluated in vivo using C57BL/6 (wide-type) mice (n=32) and granulocyte macrophage colony-stimulating factor knock out (GM-CSF-/-) mice (n=32). PE-only (n=8), plasma immersion ion implantation treated PE (PIII) (n=8), PIII with one layer TE coating PE (PIII+TE, n=8) and PIII with double layers TE coating PE (PIII+2TE, n=8) were implanted subcutaneously into the back of mice separately. However, the group of PIII+TE was excluded. Implants were harvested at weeks 1, 2, 4 and 8. In addition, GM-CSF-/- mice model was used to investigate whether GM-CSF was the key cytokine in the adjustment of foreign body reaction. Our results show that tropoelstin affects the macrophage response in host responses. PIII+2TE decreased the infiltrative numbers of macrophages (F4/80+ cells), and elevated the percentage of M2 cells (F4/80+Ym-1+Arg-1+ cells) compared to PE-only during the acute inflammation. In addition, lower levels of macrophages with higher proportion of M2 cells were observed in GM-CSF-/- mice among three biomaterials. Based on the previous results, this study further demonstrated that PE with PIII+2TE modification can mitigate inflammatory response, defined mainly by higher number of M2 cells in the capsule of implantation. It also indicated that the deficiency of GM-CSF influenced the infiltration and M2 polarisation of macrophage. In conclusion, tropoelastin was assumed to elevate M2 percentage at the site of implantation via downregulation of GM-SCF. However, further investigations are needed to elucidate the downstream of GM-CSF in the polarisation of macrophage.