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Polypropylene mesh implantation for hernia repair causes myeloid cell–driven persistent inflammation
Felix Heymann, … , Ulf P. Neumann, Frank Tacke
Felix Heymann, … , Ulf P. Neumann, Frank Tacke
Published January 24, 2019
Citation Information: JCI Insight. 2019;4(2):e123862. https://doi.org/10.1172/jci.insight.123862.
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Research Article Gastroenterology Inflammation

Polypropylene mesh implantation for hernia repair causes myeloid cell–driven persistent inflammation

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Abstract

Polypropylene meshes that are commonly used for inguinal hernia repair may trigger granulomatous foreign body reactions. Here, we show that asymptomatic patients display mesh-associated inflammatory granulomas long after surgery, which are dominated by monocyte-derived macrophages expressing high levels of inflammatory activation markers. In mice, mesh implantation by the onlay technique induced rapid and strong myeloid cell accumulation, without substantial attenuation for up to 90 days. Myeloid cells segregated into distinct macrophage subsets with separate spatial distribution, activation profiles, and functional properties, showing a stable inflammatory phenotype in the tissue surrounding the biomaterial and a mixed, wound-healing phenotype in the surrounding stromal tissue. Protein mass spectrometry confirmed the inflammatory nature of the foreign body reaction, as characterized by cytokines, complement activation, and matrix-modulating factors. Moreover, immunoglobulin deposition increased over time around the implant, arguing for humoral immune responses in association with the cell-driven inflammation. Intravital multiphoton microscopy revealed a high motility and continuous recruitment of myeloid cells, which is partly dependent on the chemokine receptor CCR2. CCR2-dependent macrophages are particular drivers of fibroblast proliferation. Thus, our work functionally characterizes myeloid cell–dependent inflammation following mesh implantation, thereby providing insights into the dynamics and mechanisms of foreign body reactions to implanted biomaterials.

Authors

Felix Heymann, Klaus-Thilo von Trotha, Christian Preisinger, Petra Lynen-Jansen, Anjali A. Roeth, Melanie Geiger, Lukas Jonathan Geisler, Anna Katharina Frank, Joachim Conze, Tom Luedde, Christian Trautwein, Marcel Binnebösel, Ulf P. Neumann, Frank Tacke

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Figure 5

Protein expression analysis of inflammation-associated factors from murine mesh explants.

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Protein expression analysis of inflammation-associated factors from muri...
Protein mass spectrometry analysis of tissue isolated from mesh- and sham-operated animals at day 7 and day 21. (A) Venn diagram showing differential protein signatures. Overlapping areas show proteins coidentified at the corresponding conditions. (B) Scatter plot displaying weighted protein expression of mesh and sham isolated tissue. Total protein counts of all samples (sum) were plotted on that y axis, weighted protein expression was displayed as log2-fold expression ratio. Signature proteins of GO pathways described in C were highlighted in the corresponding colors. (C) Cluster network analysis using BinGO (55) to determine clusters enriched in mesh-associated tissue at day 7. Protein expression was calculated against corresponding sham-operated controls with n = 3 animals per group. (D) String protein interaction network analysis. Proteins expressed with a log2 fold ratio of >4 in mesh versus sham samples at day 7 were filtered for generalized pathways relevant for inflammation, immune system activation, and wound healing. Relevant protein networks and exemplary targets are shown.

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