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Updated: Aug 8, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
M1 and M2 macrophages markers are alternately expressed during periapical lesion development
Carolina Maschietto Pucinelli1, Paulo Nelson-Filho1, Marília Pacífico Lucisano1
1Universidade de São Paulo, Faculdade de Odontologia de Ribeirão Preto, Departamento de Clínica Infantil, Ribeirão Preto, SP, Brasil.
Background:
This study evaluated the altered expression levels of genes and cytokines associated with M1 and M2 macrophages during the development of periapical lesion (PL).
Methodology:
PL was induced in the lower first molars of 96 mice. After the experimental periods of two, seven, 14, 21, and 42 days, the animals were euthanized and their jaws were dissected and submitted to the following analyses: microscopic descriptive analysis and fluorescence microscopy morphometry of PL size (mm2); quantitative gene expression analysis by qRT-PCR for M1 (Cxcl10, Cxcl9, and Nos2) and M2 phenotypes (Arg1, Fizz1, Ym1, and Mrc1); and M1- (GM-CSF, IFN-γ, IL-6, IL-1β, TNF-α) and M2- (IL-4, IL-13, and IL- 10) related cytokines quantification by Luminex. Data were statistically compared by ANOVA, Tukey post-test, Kruskal-Wallis, and Dunn post-test (α=5%).
Results:
PL area and inflammatory infiltrate increased over experimental periods. From a contextual view, a pro-inflammatory profile and a higher activation of M1 phenotype markers in the initial periods of two and seven days could be observed. On day 21, microscopic features and M2 subtype predominance indicated a repair attempt. However, on day 42, an acute exacerbation of immunoinflammatory process and return to the M1 macrophage profile were evidenced.
Conclusion:
M1 and M2 macrophage polarization-related markers were expressed alternately throughout the experimental periods, according to the stage of PL progression.
Insights
Periapical lesion (PL) development involves dynamic shifts between M1 and M2 macrophage profiles. This study tracks these changes, revealing an initial M1 dominance followed by an M2-mediated repair attempt, and a later M1 resurgence.
Area of Science:
- Oral biology
- Immunology
- Pathology
Background:
- Periapical lesions (PL) involve complex immune responses.
- Macrophage polarization into M1 (pro-inflammatory) and M2 (anti-inflammatory/repair) phenotypes plays a critical role in lesion development and resolution.
Purpose of the Study:
- To investigate the dynamic expression of M1 and M2 macrophage markers during periapical lesion progression in a mouse model.
- To correlate macrophage polarization with the stages of periapical lesion development and inflammatory processes.
Main Methods:
- Induction of periapical lesions in mice, followed by analysis at multiple time points (2, 7, 14, 21, and 42 days).
- Assessment of lesion size and inflammatory infiltrate using microscopy.
- Quantitative gene expression analysis of M1 (Cxcl10, Cxcl9, Nos2) and M2 (Arg1, Fizz1, Ym1, Mrc1) markers via qRT-PCR.
- Cytokine profiling for M1 (GM-CSF, IFN-γ, IL-6, IL-1β, TNF-α) and M2 (IL-4, IL-13, IL-10) using Luminex assays.
Main Results:
- Periapical lesion area and inflammation increased over time.
- An initial pro-inflammatory M1 macrophage dominance was observed at early stages (days 2-7).
- A shift towards M2 macrophage markers indicating a repair attempt occurred by day 21, but this was followed by a resurgence of the M1 profile and exacerbated inflammation by day 42.
Conclusions:
- Macrophage polarization is a dynamic process during periapical lesion development.
- The balance between M1 and M2 macrophage phenotypes shifts according to the stage of the periapical lesion, influencing the inflammatory and repair processes.
