Effects of particulate debris on macrophage-dependent fibroblast stimulation in coculture

Abstract

The interactions between the different cell types in periprosthetic tissue are still unclear. We used a non-contact coculture model to investigate the effects of polymethylmethacrylate (PMMA) particles and human macrophage-derived soluble mediators on fibroblast activation. Macrophages were either exposed or not exposed to phagocytosable PMMA particles, but fibroblasts were not. Increasing numbers of macrophages were tested in cocultures in which the fibroblast cell number was held constant and cultures of macrophages alone were used for comparison of cytokine release. We used the release of interleukin-1 beta (IL-1␤), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-␣), lysosomal enzyme and metalloproteinase activity to assess the cultivation of macrophages and fibroblasts.In cocultures, IL-6 release was increased 100-fold for both unchallenged and particle-challenged cultures when compared with macrophage cultures alone. Furthermore, particle-challenged cocultures had threefold higher IL-6 levels than unchallenged cocultures. Release of TNF-␣ was similar in cocultures and in macrophage cultures. IL-1␤ release in cocultures was independent of the macrophage-fibroblast ratio. Lysosomal enzyme activity and metalloproteinase activity were increased in cocultures.Our data show that macrophages and fibroblasts in coculture significantly increase the release of IL-6 and to a less degree other inflammatory mediators; particle exposure accentuates this effect. This suggests that macrophage accumulation in fibrous tissue may lead to elevated IL-6 levels that are much higher than those caused by particle activation of macrophages alone. This macrophage-fibroblast interaction represents a novel concept for the initiation and maintenance of the inflammatory process in periprosthetic membranes.J Bone Joint Surg [Br] 1998;80-B:924-30.

IL-1β as a determinant in silica-induced cytokine responses in monocyte-endothelial cell co-cultures

“…43 A non-contact co-culture of macrophages and fibroblasts showed a marked increase of IL-1β and IL-6, but not of TNF-α release, compared with macrophages alone after exposure to polymethylmetachrylate particles. 41 Interestingly, this study showed a similar pattern to our findings in the monocyte/endothelial cell co-culture system. However, other co-culture studies with different agents, including particles, demonstrate absence of enhanced stimulation compared with mono-cultures.…”

“…36,40,41 Figure 2 shows the effect of exposure to silica for 43 h on the release of TNF-α, IL-1β, IL-6, and IL-8 from the mono-and cocultures. Figure 3 shows silica-induced release of IL-4, IL-10 and TGF-β from these cultures.…”

Cyclosporine‐A inhibits MMP‐2 and ‐9 activities in the presence of Porphyromonas gingivalis lipopolysaccharide: an experiment in human gingival fibroblast and U937 macrophage co‐culture

“…As the interleukin‐6 released by the gingival fibroblasts was essential for the augmentation of MMP‐1 expression by the macrophages, cross‐talk between the two types of cells exposed to high glucose was proposed by the authors. Another study, using co‐culture, found that the release of interleukin‐6 was increased 100‐fold when compared with that using culture of macrophages alone (30).…”

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

“…The release of macrophage chemoattractants from fibroblasts further supports the relationship and synergism that may occur between macrophages and fibroblasts in the periprosthetic membrane. Lind et al reported that fibroblasts and macrophages exposed to titanium particles in coculture increase the release of IL-6 by a 100-fold when compared to macrophage cultures alone [18]. Zickus et al reported increased production of MCP-1 and MIP-I alpha from fibroblast-macrophage cocultures as well [45].…”