Lymphocytes and the foreign body response: Lymphocyte enhancement of macrophage adhesion and fusion

Abstract

The host foreign body response ensues immediately following implantation of medical devices and prostheses. We have previously identified the role of macrophages in adhering to biomaterial surfaces and guiding the foreign body response while fusing into foreign body giant cells (FBGCs) and concentrating degradative and phagocytic activities. Despite their early and transient presence around implanted biomaterials, few studies have focused on the role of lymphocytes in the foreign body response and biocompatibility. To address this, an in vitro human lymphocyte/macrophage coculture system has been developed. Using this system, it has been shown that when lymphocytes are present during the initial adhesion of monocytes, the rate of monocyte adhesion and fusion is significantly increased (1,500 cells/mm2 and 60%, respectively) when compared to either no lymphocytes present (500 cells/mm2 adhesion and 0% fusion). Although lymphocytes adhered to the tissue culture polystyrene surface, 90% of the lymphocytes were associated with adherent macrophages. However, these cell-cell direct interactions were not necessary to influence macrophage adhesion or fusion as separating the two cell types by a Transwell insert still resulted in significantly increased levels of macrophage adhesion (p < 0.05 when compared to macrophage only cultures). Conversely, the presence of macrophages in Transwell experiments increased lymphocyte proliferation rates at all time points tested. These studies begin to detail the interactions between lymphocytes and macrophages in the absence of known antigen that appropriately relates to the scenarios experienced upon implantation of biomedical devices and the initiation of the foreign body response.

Cellular Plasticity of Inflammatory Myeloid Cells in the Peritoneal Foreign Body Response

“…This finding is in agreement with results of other studies demonstrating the involvement of lymphocytes in the tissue response to foreign materials. [33][34][35] We demonstrate that implantation of sterile foreign objects in the peritoneal cavity initiates an inflammatory response in which EGFP ϩ Gr1 ϩ (Ly6C ϩ ) monocytes and granulocytes are rapidly recruited to the peritoneal cavity and encapsulate the foreign object. Morphological analysis shows that the EGFP ϩ Gr1 ϩ (Ly6C ϩ ) cells, which enter the peritoneal cavity and encapsulate the implanted object in the early phase (at day 2), are primarily granulocytes, with monocytes representing only a minor subset.…”

Systemic and Local Tissue Response to Titanium Corrosion

“…Particles that are smaller than the macrophages themselves (< 10 µm) can be easily phagocytosed. However, the larger particles (10-100 µm) are ingested by giant, multinucleate cells (Brodbeck et al, 2005). The biokinetics of TiO 2 and ZrO 2 microparticles depends on differences in physicochemical properties of the particles, such as size, shape and/or crystal structure (Olmedo et al, 2011).…”

Foreign Body Giant Cell Formation Is Preceded by Lamellipodia Formation and Can Be Attenuated by Inhibition of Rac1 Activation

“…29 Previous studies investigating fusion have noted the occurrence of cytoskeletal changes similar to those observed in phagocytosis. 13,30 Although the rearrangement of the cell's cytoskeleton is an important component of both phagocytosis and fusion, the role of lamellipodia formation in fusion has not been previously reported. Consistent with the vital role of Rac1 in lamellipodia formation, 31 we observed Rac1 activation in IL-4-treated cells before changes in cell shape.…”