Synergistic induction of cyclooxygenase-II by bacterial lipopolysaccharide in combination with particles of medical device materials in a murine macrophage cell line J774A.1

Abstract

Corrosion and wear of implanted medical devices may produce particulate debris, leading to acute and chronic inflammatory responses in the host. In the presence of biomaterial wear particles, host monocytes/macrophages are activated to synthesize or secrete mediators of inflammation. In order to understand the mechanisms underlying the host response to particulates and device-associated infections, we have focused on the effects of medical device particles on macrophage function, because these cells play a pivotal role in the body's response to foreign bodies and their interaction with other cellular components of the immune system. In order to evaluate the effects of particles of medical device materials on functional activities of macrophages, we developed a cyclooxygenase-II (COX-II) assay system using J774A.1 macrophages. Constitutive cyclooxygenase (COX-I) is present in cells under physiological conditions, whereas inducible COX-II is induced by some cytokines, mitogens, and endotoxin, presumably in pathological conditions such as inflammation. We have evaluated the inductive effects of implant materials, i.e., particles of polymethylmethacrylate (PMMA), hydroxyapatite (HA), titanium oxide, and silica, on the activity of COX-II using thin layer chromatography of prostaglandin D(2) (PGD(2)) formed from [1-(14)C]-labeled arachidonic acid (AA). Also, we have assessed the synergistic effects of these particles on lipopolysaccharide (LPS)-mediated macrophage activation. Addition of LPS to these particles increased PGD(2) production several-fold greater than the addition of any inducer alone. Our results indicated that device-associated infections could enhance inflammatory responses to the wear particles in subjects with medical implants or in whom particulate biomaterials are used for clinical purposes. The use of this model COX-II assay system may lead to the identification of inflammatory potentials for implant materials more specifically than present in vivo assays.

Potential proinflammatory and osteogenic effects of dicalcium silicate particles in vitro

“…Thus, a direct crystal-cell membrane interaction is the main mechanism by which the cells are stimulated [41] . Although some studies have shown that endocytosis induces the synthesis of metalloproteinases, collagenase and stromelysin [42] , other reports have indicated that non-phagocytosable particles cause increased MMP-9 production [22] .…”

Does endotoxin contribute to aseptic loosening of orthopedic implants?

“…These studies have examined activation of signal transduction pathways, 40 -42 metabolic activity, 43 and production of proinflammatory cytokines 41,[43][44][45][46][47] and have examined virtually all orthopedically relevant types of particles, including titanium, 42,44,47 cobaltchrome, [43][44][45] PMMA, 40,42,46 polyethylene, 43,45 and hydroxyapatite. 42 Most importantly, Akisue et al 41 have further extended these studies to include authentic titanium alloy particles retrieved from patients with aseptic loosening.…”

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

“…2,3 Macrophages can phagocytose wear debris derived from implant materials and produce various pro-inflammatory cytokines to induce periprosthetic osteolysis, thus contributing to aseptic loosening of THA implants. [1][2][3][4][5][6][7] Toll-like receptors (TLRs) and nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) have been reported to contribute to the pathogenesis of osteolysis induced by implant wear particles. [8][9][10][11][12] Expression of TLR2, TLR4, TLR5, and TLR9 is increased in macrophages in aseptic periprosthetic tissues of loose implants.…”