Maria Elisa Galarraga-Vinueza1,2,3, Karina Obreja1, Ausra Ramanauskaite1, Ricardo Magini2, Amira Begic1, Robert Sader4, Frank Schwarz5,6. 1. Department of Oral Surgery and Implantology, Johann Wolfgang Goethe-University, Carolinum, Frankfurt, Germany. 2. Post-Graduate Program in Implant Dentistry (PPGO), Federal University of Santa Catarina (UFSC), Florianopolis, SC, Brazil. 3. School of Dentistry, Universidad de Las Américas, Quito, Ecuador. 4. Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University Frankfurt, Frankfurt am Main, Germany. 5. Department of Oral Surgery and Implantology, Johann Wolfgang Goethe-University, Carolinum, Frankfurt, Germany. f.schwarz@med.uni-frankfurt.de. 6. Department of Oral Surgery, Universitätsklinikum Düsseldorf, Dusseldorf, Germany. f.schwarz@med.uni-frankfurt.de.
Abstract
OBJECTIVES: To immunohistochemically characterize and correlate macrophage M1/M2 polarization status with disease severity at peri-implantitis sites. MATERIALS AND METHODS: A total of twenty patients (n = 20 implants) diagnosed with peri-implantitis (i.e., bleeding on probing with or without suppuration, probing depths ≥ 6 mm, and radiographic marginal bone loss ≥ 3 mm) were included. The severity of peri-implantitis was classified according to established criteria (i.e., slight, moderate, and advanced). Granulation tissue biopsies were obtained during surgical therapy and prepared for immunohistological assessment and macrophage polarization characterization. Macrophages, M1, and M2 phenotypes were identified through immunohistochemical markers (i.e., CD68, CD80, and CD206) and quantified through histomorphometrical analyses. RESULTS: Macrophages exhibiting a positive CD68 expression occupied a mean proportion of 14.36% (95% CI 11.4-17.2) of the inflammatory connective tissue (ICT) area. Positive M1 (CD80) and M2 (CD206) macrophages occupied a mean value of 7.07% (95% CI 5.9-9.4) and 5.22% (95% CI 3.8-6.6) of the ICT, respectively. The mean M1/M2 ratio was 1.56 (95% CI 1-12-1.9). Advanced peri-implantitis cases expressed a significantly higher M1 (%) when compared with M2 (%) expression. There was a significant correlation between CD68 (%) and M1 (%) expression and probing depth (PD) values. CONCLUSION: The present immunohistochemical analysis suggests that macrophages constitute a considerable proportion of the inflammatory cellular composition at peri-implantitis sites, revealing a significant higher expression for M1 inflammatory phenotype at advanced peri-implantitis sites, which could possibly play a critical role in disease progression. CLINICAL RELEVANCE: Macrophages have critical functions to establish homeostasis and disease. Bacteria might induce oral dysbiosis unbalancing the host's immunological response and triggering inflammation around dental implants. M1/M2 status could possibly reveal peri-implantitis' underlying pathogenesis.
OBJECTIVES: To immunohistochemically characterize and correlate macrophage M1/M2 polarization status with disease severity at peri-implantitis sites. MATERIALS AND METHODS: A total of twenty patients (n = 20 implants) diagnosed with peri-implantitis (i.e., bleeding on probing with or without suppuration, probing depths ≥ 6 mm, and radiographic marginal bone loss ≥ 3 mm) were included. The severity of peri-implantitis was classified according to established criteria (i.e., slight, moderate, and advanced). Granulation tissue biopsies were obtained during surgical therapy and prepared for immunohistological assessment and macrophage polarization characterization. Macrophages, M1, and M2 phenotypes were identified through immunohistochemical markers (i.e., CD68, CD80, and CD206) and quantified through histomorphometrical analyses. RESULTS: Macrophages exhibiting a positive CD68 expression occupied a mean proportion of 14.36% (95% CI 11.4-17.2) of the inflammatory connective tissue (ICT) area. Positive M1 (CD80) and M2 (CD206) macrophages occupied a mean value of 7.07% (95% CI 5.9-9.4) and 5.22% (95% CI 3.8-6.6) of the ICT, respectively. The mean M1/M2 ratio was 1.56 (95% CI 1-12-1.9). Advanced peri-implantitis cases expressed a significantly higher M1 (%) when compared with M2 (%) expression. There was a significant correlation between CD68 (%) and M1 (%) expression and probing depth (PD) values. CONCLUSION: The present immunohistochemical analysis suggests that macrophages constitute a considerable proportion of the inflammatory cellular composition at peri-implantitis sites, revealing a significant higher expression for M1 inflammatory phenotype at advanced peri-implantitis sites, which could possibly play a critical role in disease progression. CLINICAL RELEVANCE: Macrophages have critical functions to establish homeostasis and disease. Bacteria might induce oral dysbiosis unbalancing the host's immunological response and triggering inflammation around dental implants. M1/M2 status could possibly reveal peri-implantitis' underlying pathogenesis.
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