Accumulation and localization of macrophage phenotypes with human intervertebral disc degeneration

Publication date: Available online 12 October 2017
Source:The Spine Journal
Author(s): Kenneth R. Nakazawa, Benjamin A. Walter, Damien M. Laudier, Divya Krishnamoorthy, Grace E. Mosley, Kara L. Spiller, James C. Iatridis
Background ContextChronic inflammation is an important component of intervertebral disc (IVD) degeneration, but there is limited knowledge about the identity and source of inflammatory cells involved with the degenerative processes. Macrophages can exhibit multiple phenotypes and are known inflammatory regulators in many tissues, but their phenotypes have not been characterized in IVD degeneration.PurposeTo characterize accumulation and localization of macrophages in IVD degeneration.Study Design/SettingExploratory study to characterize macrophage phenotypes in human cadaver IVDs and the effects of injury and degeneration using multiple immunohistochemistry methods.Patient SampleN.A.Outcome Measures% Positivity of immunohistochemical markers specific for CCR7, CD163 and CD206. Qualitative assessments of dual immunofluorescence and immunostaining localization.MethodsMacrophages were identified in human cadaveric IVDs with immunohistochemistry using cell surface markers CCR7, CD163, and CD206, which are associated with pro-inflammatory M1, remodeling M2c, and anti-inflammatory M2a phenotypes, respectively. Variations in the accumulation and localization of macrophage markers with degenerative grade across subjects and within donors are described. Federal grant funded project with no relevant conflicts.ResultsCells expressing all three macrophage markers were found in all degenerative IVDs, but not in the healthiest IVDs. Cells expressing CCR7 and CD163, but not CD206 significantly increased with degenerative grade. Many cells also coexpressed multiple macrophage markers. Across all degenerative grades, CCR7+ and CD163+ were significantly more present in unhealthy NP, AF, and EP regions exhibiting structural irregularities and defects. Positively stained cells in the NP and AF closely resembled resident IVD cells, suggesting that IVD cells can express macrophage cell surface markers. In the EP, there were increasing trends of positively stained cells with atypical morphology and distribution, suggesting a source for exogenous macrophage infiltration into the IVD.ConclusionsChronic inflammatory conditions of IVD degeneration appear to involve macrophages or macrophage-like cells, as expression of multiple macrophage markers increased with degeneration, especially around unhealthy regions with defects and the EP. Knowledge of macrophage phenotypes and their localization better elucidates the complex injury and repair processes in IVDs and may eventually lead to novel treatments.



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