Induction of macrophage C-C chemokine expression by titanium alloy and bone cement particles

Abstract

Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1␣), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration.We observed MCP-1 and MIP-1␣ expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1␣ in macrophages in vitro in a dose-and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1␣ were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1␣ inhibited chemotactic activity of the culture medium samples.Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty.J Bone Joint Surg [Br] 1999;81-B:155-62.

Fibroblast expression of C—C chemokines in response to orthopaedic biomaterial particle challenge in vitro

“…MCP-1 and MIP-I alpha are found in membranes retrieved from failed TJA [27]. In vitro analysis has identified macrophages exposed to particulate debris as one possible source of MCP-1 and MIP-1 alpha [17,27].…”

“…In vitro analysis has identified macrophages exposed to particulate debris as one possible source of MCP-1 and MIP-1 alpha [17,27]. However, the effect of particles on fibroblast release of macropliage chemoattractant factors remains unknown.…”

How Has the Introduction of New Bearing Surfaces Altered the Biological Reactions to Byproducts of Wear and Modularity?

“…Studies have also shown a variety of cell signaling pathways are involved in the cellular response to debris. These include mitogenactivated protein kinase activation [1], induction of granulocyte macrophage colony-stimulating factor [6], C-C chemokine expression [55], matrix metalloproteinase induction [56], NFkB activation [59,66,72], nitric oxide elicitation [45,64,75], induction of apoptosis [74], cytokine activation [43,78], and direct activation of cyclooxygenase-2 [82]. Although most studies on the etiology of aseptic loosening have been focused on macrophage as the central cell of interest, there is recent interest in examining the role of the fibroblasts in the MMPs 56 UHMWPE = ultrahigh-molecular-weight polyethylene; IL = interleukin; TNF = tumor necrosis factor; GM-CSF = granulocyte macrophage colony-stimulating factor; MMPs = matrix metalloproteinases.…”

Is Monocyte Chemotactic Protein 1 Elevated in Aseptic Loosening of TKA?: A Pilot Study

“…While several in vitro studies have examined the role of monocyte chemotactic protein 1 (MCP-1) in the synovial tissues of patients with chronic wear debris-induced inflammation [6,7,11,19,24,36], none assessed MCP-1 in synovial fluid of patients undergoing TKA revision surgery for aseptic loosening. Collectively, these in vitro studies demonstrate increased MCP-1 gene expression and protein associated with chronic wear debris.…”

“…Collectively, these in vitro studies demonstrate increased MCP-1 gene expression and protein associated with chronic wear debris. These studies focused on titanium [6,7] and polymethylmethacrylate particles [24]. Fritz et al [6,7] performed analyses with human bone marrow-derived and osteosarcoma cells.…”