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Macrophage polarization differs between apical granulomas, radicular cysts, and dentigerous cysts

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Abstract

Objectives

Apical periodontitis can appear clinically as apical granulomas or radicular cysts. There is evidence that immunologic factors are involved in the pathogenesis of both pathologies. In contrast to radicular cysts, the dentigerous cysts have a developmental origin. Macrophage polarization (M1 vs M2) is a main regulator of tissue homeostasis and differentiation. There are no studies comparing macrophage polarization in apical granulomas, radicular cysts, and dentigerous cysts.

Materials and methods

Forty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray (TMA) of the 87 consecutive specimens was created, and CD68-, CD11c-, CD163-, and MRC1-positive macrophages were detected by immunohistochemical methods. TMAs were digitized, and the expression of macrophage markers was quantitatively assessed.

Results

Radicular cysts are characterized by M1 polarization of macrophages while apical granulomas show a significantly higher degree of M2 polarization. Dentigerous cysts have a significantly lower M1 polarization than both analyzed periapical lesions (apical granulomas and radicular cysts) and accordingly, a significantly higher M2 polarization than radicular cysts. Macrophage cell density in dentigerous cysts is significantly lower than in the periapical lesions.

Conclusions

The development of apical periodontitis towards apical granulomas or radicular cysts might be directed by macrophage polarization. Radicular cyst formation is associated with an increased M1 polarization of infiltrating macrophages. In contrast to radicular cysts, dentigerous cysts are characterized by a low macrophage infiltration and a high degree of M2 polarization, possibly reflecting their developmental rather than inflammatory origin.

Clinical relevance

As M1 polarization of macrophages is triggered by bacterial antigens, these results underline the need for sufficient bacterial clearance during endodontic treatment to prevent a possible M1 macrophage-derived stimulus for radicular cyst formation.

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Acknowledgements

The authors thank Luitpold Distel for his assistance in the cell counting procedure. The authors also thank Christian Dittmann for providing the vector graphics for Fig. 5. We would like to thank Rudolf Jung for manufacturing the TMAs and Susanne Schoenherr and Elke Diebel for technical assistance. We would also like to thank the dental student Lena Marsing for processing the tissue specimens and operating the immunohistochemistry autostainer apparatus.

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Authors and Affiliations

Authors

Contributions

The authors’ initials are used.

MW formulated the hypothesis, initiated and conducted the study, interpreted the data, and wrote the manuscript. FW formulated the hypothesis, conducted the study, interpreted the data, and contributed relevantly to the manuscript. TS selected the patient collective, analyzed the medical records, interpreted the data and contributed to the manuscript. PM performed the immunohistochemical analyses and the whole slide imaging of the specimens, helped with cell counting, and critically reviewed the manuscript. MB and JR helped validate the markers, contributed to the discussion, and critically reviewed the manuscript. FN and RP contributed to the discussion and critically reviewed the manuscript.

All of the authors read and approved the final manuscript.

Corresponding author

Correspondence to Manuel Weber.

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Conflict of interest

The authors declare that they have no conflict of interest.

Funding

The study was self-funded by the authors and their institutions.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study, formal consent is not required.

Additional information

This study was not financially supported by a third party.

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Weber, M., Schlittenbauer, T., Moebius, P. et al. Macrophage polarization differs between apical granulomas, radicular cysts, and dentigerous cysts. Clin Oral Invest 22, 385–394 (2018). https://doi.org/10.1007/s00784-017-2123-1

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  • DOI: https://doi.org/10.1007/s00784-017-2123-1

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