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Updated: Jul 10, 2026

An In vitro Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization
Published on: June 12, 2013
Exploring macrophage differentiation and its relation to Modic changes in human herniated disc tissue
N Djuric1,2, G C M Lafeber1,2, W Li1,2
1University Neurosurgical Center Holland, the Netherlands.
Introduction:
Cervical- and lumbosacral radiculopathy symptoms due to disc herniation are likely to be influenced by macrophage infiltration of the herniated disc. Vertebral endplate changes are hypothesized to, at least partially, correlate to the inflammatory condition of the disc and its environment.
Research Question:
The present study aims to evaluate several immunohistochemical M1-and M2-markers for their suitability to discern pro-inflammatory M1-and anti-inflammatory M2 macrophage differentiation patterns in herniated intervertebral disc tissue. In addition, their associations with Modic changes (MC) of the vertebral endplates will be evaluated.
Materials And Methods:
Herniated disc samples were collected from 45 patients undergoing surgery for cervical- or lumbosacral radiculopathy. Samples were processed for immunohistochemistry and stained for the presence of macrophages: CD68 (macrophage marker), CD40 (M1), iNOS (M1), CD192 (M1), CD163 (M2), Arg1 (M2) and CD209 (M2). T-cells (CD3) and neutrophil (CD15) expressions were studied additionally.
Results:
CD68 positive cells were present with a median density of 50/cm2, M2 markers CD163 and CD209 were expressed most dominantly, followed by M1 marker CD192. Other M1/M2 markers, T-cell and neutrophil expression was limited. Lumbar samples showed higher expression of iNOS and Arg1 compared to cervical samples. Presence of Modic changes was associated with higher levels of CD68+ cells (p = 0.046), but no significant differences in M1/M2 markers were found.
Discussion And Conclusion:
For studying M1 macrophages, CD192 is the most suitable marker due to its high expression; whereas for M2 macrophages, this is CD163 due to its high expression and selectivity. Further, the relatively high expression of M2 markers indicates predominance of anti-inflammatory over pro-inflammatory macrophages in symptomatic lumbar and cervical disc herniations. No associations between M1/M2 markers and MC were seen in this limited number of samples. In order to further explore the role of macrophage differentiation and its relation with MC in radiculopathy, a large prospective trial with elaborate clinical follow-up is required.
Insights
Macrophage infiltration influences disc herniation symptoms. This study found anti-inflammatory M2 macrophages dominate in herniated discs, with CD163 being a key marker, while Modic changes showed no direct link to macrophage types.
Area of Science:
- Immunology
- Orthopedics
- Pathology
Background:
- Macrophage infiltration is implicated in cervical and lumbosacral radiculopathy caused by disc herniation.
- Vertebral endplate changes, such as Modic changes (MC), may correlate with the disc's inflammatory state.
Purpose of the Study:
- To assess immunohistochemical markers for differentiating M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages in herniated disc tissue.
- To investigate the association between macrophage differentiation patterns and Modic changes in the vertebral endplates.
Main Methods:
- Analyzed 45 herniated disc samples from patients with radiculopathy using immunohistochemistry.
- Stained for macrophage markers (CD68), M1 markers (CD40, iNOS, CD192), M2 markers (CD163, Arg1, CD209), T-cells (CD3), and neutrophils (CD15).
Main Results:
- CD68+ cells were present; M2 markers (CD163, CD209) showed higher expression than M1 markers (CD192).
- Lumbar samples exhibited greater iNOS and Arg1 expression than cervical samples.
- Modic changes correlated with higher CD68+ cell density, but not significantly with specific M1/M2 marker expression.
Conclusions:
- CD192 and CD163 are suitable markers for M1 and M2 macrophages, respectively.
- Symptomatic disc herniations show a predominance of anti-inflammatory M2 macrophages.
- Further large-scale studies are needed to clarify the relationship between macrophage differentiation and Modic changes in radiculopathy.
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