title: Costimulatory molecule expression following exposure to orthopaedic implants wear debris.
abstract: Patients with long-term orthopedic implants may develop inflammatory reactions due to the accumulation of biomaterial particles both around the implant 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 particles is driven by macrophages and requires synergistic signals primed by both antigen presentation and costimulation. The pattern of costimulatory molecule expression (CD80,CD86) was primarily examined using immunohistochemistry on tissue specimens of bone/implant interface membranes taken from sites of bone erosion. Additionally, costimulatory 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 fused forms and large multinucleated giant cells (MNGC). In vitro analysis also indicated phagocytosis of metal particles by differentiated U937 caused significant induction of both CD80 and CD86 (p < 0.01), although the expression of CD86 dominated following prolonged exposure. The data presented highlights that CD86 is the predominant costimulatory molecule ligating to the complementary CD28 molecule at the inflammatory lesion of the interface. We propose that the intracellular presence of indigestible implant material, in addition to elevated costimulatory molecule expression, may promote T-cell inflammatory reactions at sites close to and distant from the orthopedic implant.
authors.affiliation: Department of Histopathology, Royal Free and University College Medical School, Hampstead, London, United Kingdom.
authors.forename: J A
authors.initials: JA
authors.lastname: Bainbridge
authors.forename: P A
authors.initials: PA
authors.lastname: Revell
authors.forename: N
authors.initials: N
authors.lastname: Al-Saffar
mesh_terms: D000497:Alloys / Q000633:toxicity; D018122:B7-1 Antigen / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D019736:Prostheses and Implants / Q000009:adverse effects*; D014025:Titanium / Q000633:toxicity
chemical_list: D000497:Alloys; D018122:B7-1 Antigen; C031462:titanium alloy (TiAl6V4); D014025:Titanium