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Updated: Aug 16, 2025
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
CCL3 aggravates intestinal damage in NEC by promoting macrophage chemotaxis and M1 macrophage polarization
1Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China.
Background:
NEC is a life-threatening gastrointestinal disease in neonates, the pathogenesis of which remains poorly understood.
Methods:
CCL3 levels in intestinal tissue of mice were measured and analyzed. HE staining was used to assess pathological changes in intestinal tissue. FCM was used to detect the proportion and phenotype of macrophages. RNA-seq and RT-PCR were used to evaluate the effect of CCL3 on macrophages.
Results:
CCL3 was highly expressed in the intestinal tissues of mice with NEC and induced macrophage infiltration. Transcriptome data showed that CCL3 strongly induced a transition in the phenotype of macrophages into a proinflammatory one. Mechanistically, in vivo experiments confirmed that CCL3 induced M1 macrophage polarization in NEC intestinal tissue, thereby aggravating inflammatory injury of intestinal tissue, which was alleviated by anti-CCL3 treatment. In addition, in vitro experiments showed that CCL3 significantly enhances the expression of M1-related genes in both PMφ and BMDM while inhibiting the expression of M2-related genes, which was also alleviated by anti-CCl3 treatment.
Conclusions:
Our data elucidated the involvement of CCL3 in the pathogenesis of NEC, in which upregulated CCL3 expression exacerbated inflammatory intestinal damage by regulating macrophage chemotaxis and M1 phenotype polarization, suggesting that blocking CCL3 may be a potential strategy for effective intervention in NEC.
Impact:
Our study represents an important conceptual advancement that CCL3 may be one of the key culprits of intestinal tissue damage in patients with NEC. CCL3 aggravates inflammatory intestinal injury and intestinal mucosal barrier imbalance by regulating the chemotaxis, polarization, and function of macrophages. Blocking CCL3 significantly reduced NEC-mediated intestinal injury, suggesting a new potential therapeutic strategy.
Insights
Chemokine (C-C motif) ligand 3 (CCL3) exacerbates necrotizing enterocolitis (NEC) by promoting M1 macrophage polarization and inflammatory injury. Blocking CCL3 offers a potential therapeutic strategy for NEC.
Area of Science:
- Immunology
- Gastroenterology
- Neonatal Research
Background:
- Necrotizing enterocolitis (NEC) is a severe neonatal gastrointestinal disease with unclear pathogenesis.
- Understanding the molecular mechanisms driving NEC is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of Chemokine (C-C motif) ligand 3 (CCL3) in the pathogenesis of NEC.
- To elucidate the mechanism by which CCL3 influences macrophage behavior in NEC.
- To evaluate the therapeutic potential of blocking CCL3 in NEC.
Main Methods:
- Analysis of CCL3 levels in mouse intestinal tissue.
- Histopathological assessment using Hematoxylin and Eosin (HE) staining.
- Flow cytometry (FCM) for macrophage characterization.
- RNA sequencing (RNA-seq) and reverse transcription polymerase chain reaction (RT-PCR) to assess gene expression changes.
Main Results:
- CCL3 expression is elevated in NEC intestinal tissue, correlating with macrophage infiltration.
- CCL3 promotes M1 macrophage polarization, exacerbating inflammatory injury.
- In vitro and in vivo studies confirm CCL3's role in enhancing M1 and inhibiting M2 macrophage phenotypes.
- Anti-CCL3 treatment significantly alleviates NEC-induced intestinal damage.
Conclusions:
- Upregulated CCL3 contributes to NEC pathogenesis by driving macrophage recruitment and M1 polarization.
- Targeting CCL3 represents a promising therapeutic strategy for mitigating inflammatory intestinal damage in NEC.
- This study advances the understanding of NEC pathophysiology and identifies a potential therapeutic target.
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