Costimulatory molecule expression following exposure to orthopaedic implants wear debris

Patients with long-term orthopedic implants may develop inflammatory reacti ons due to the accumulation of biomaterial particles both around the implan t and in distant organs. The exact impact of these particles on the normal immune cell function still remain relatively unclear. Activation of T-cells following exposure to biomaterial par tides is driven by macrophages and r equires synergistic signals primed by both antigen presentation and costimu lation. The:pattern of costimulatory molecule expression (CD80,CD86) was pr imarily examined using immunohistochemistry on tissue specimens of bone/imp lant interface membranes taken from sites of bone erosion. Additionally, co stimulatory molecule expression was also assessed in the monocytic leukemia cell Line U937 following exposure to clinically relevant titanium aluminum vanadium (TiAlV) and-stainless steel particles (FeCrNi) cultured in vitro. This study:demonstrates the induction and prominent expression of CD86 on almost all macrophage subsets at the bone/implant interface, including fuse d forms and large multinucleated giant cells (MNGC). In vitro analysis also indicated phagocytosis of metal particles by differentiated U937 caused si gnificant induction of both CD80 and CD86 (p < 0.01), although the expressi on of CD86 dominated following prolonged exposure. The data presented highl ights that CD86 is the predominant costimulatory molecule ligating to the c omplementary CD28 molecule at the inflammatory lesion of the interface. We propose that the intracellular presence of indigestible implant material, i n addition to elevated costimulatory molecule expression, may promote T-cel l inflammatory reactions at sites close to and distant from the orthopedic implant. (C) 2000 John Wiley & Sons, Inc. J Biomed Mater Res 54: 328-334, 2 001.