Toll‐like receptors in the interface membrane around loosening total hip replacement implants

Abstract

Toll-like receptors (TLRs) have been known to act as sensors of innate immunity and respond to ligands of microbial and endogenous components. Tissues and cells typical for interface membrane of foreign body reaction were analyzed to evaluate potential role of TLRs in the pathogenesis of the so called "aseptic loosening of total hip replacement." Fourteen cases of interface membrane around aseptic loose total hip replacement implants were stained by single and double immunohistochemical methods to examine cellular localization of toll-like receptor (TLR)-4 and TLR-9. Osteoarthritic synovium was used as control tissues. Cultured macrophages were used to study TLR-4 and TLR-9 mRNA levels by quantitative reverse transcriptase-polymerase chain reaction. The effect of titanium particle stimulation on macrophages was also examined in the culture. Extensive immunolocalization of TLR-4 and TLR-9 positive cells was observed in the synovial membrane-like interface membrane of foreign body granulomas compared with control synovial membranes. TLR and CD68 double staining demonstrated that the TLR positive cells in aseptic loosening were mostly monocyte/macrophages and foreign body giant cells. TLR-4 and TLR-9 mRNA expression was also found in macrophage-colony stimulating factor treated rat macrophages, but this expression decreased (p < 0.05 or less) upon stimulation with titanium particles although matrix metalloproteinase (MMP)-9 mRNA levels used as macrophage activation marker were increased (p = 0.01). The interface membrane around loosening total hip replacement implants is apparently well equipped with TLRs and, thus, probably very sensitive to various structural components of microbes and to endogenous TLR ligands. This seems to be due to recruitment of monocyte/macrophages as particles per se seemed to down-regulate some of the key TLRs. This suppression after particle phagocytosis might prevent excessive and harmful host responses, and injury to innocent bystander cells/tissues.

Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll‐like receptor 2 cascade and inflammasomes

“…8,33,34 The NLRP3 inflammasomes activates pro-IL-1b FIGURE 2. Colocalization of TLR2, NLRP3, TNF-a, and IL-1b with CD68.…”

Aseptic Loosening of Total Hip Arthroplasty as a Result of Local Failure of Tissue Homeostasis

“…This in part, because both PAMPs and alarmins can opsonize wear particles. Various pattern recognizing receptors, such as Toll-like receptors (TLRs), mediate innate host responses and their SNPs may play a role here (Takagi et al 2007;Pajarinen et al 2010). In addition, primary and longterm fixation of the cemented and uncemented implants is dependent on the remodelling ability of the bone which is under genetic control.…”

“…This wear particle induced macrophage activation is possibly mediated by various types of cell surface pattern recognition receptors e.g. Toll-like receptors (Takagi et al 2007;Tamaki et al 2009) and likely involves the activation and action of transcription factor NF-kB (Lahdeoja et al 2010;Pearl et al 2011). The mere wear particle stimulation of pure monocyte/macrophage cultures is not sufficient to drive osteoclastogeneis or foreign body giant cell formation, most likely due to lack of RANKL signalling.…”

Inflammatory Periprosthetic Bone Loss

“…The latter interactions may include nonspecific physical induction of transmembrane proteins or recognition of cell surface molecules by particles. Recently this phenomenon was explained with the role of toll-like receptor (Takagi et al, 2007). However, the precise nature of stimulation of cells by particles remains unknown (Abu-Amer et al, 2007).…”