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Conference proceeding
Dysfunctional Macrophage Phenotype in Fibrotic Volumetric Muscle Loss Injury
01 Jan 2022
Abstract
Volumetric muscle loss (VML) is a debilitating condition resulting from the loss of a large portion soft muscle due to injury or disease. Macrophages play a crucial role in VML outcome; however, a lot is still unknown about its phenotype and interplay with other cells. We have identified systemic and local changes in immune cell trafficking, macrophage behavior and cytokine secretion in fibrotic and non-fibrotic VML injuries. Immune cell trafficking at main myeloid reservoirs (blood, bone marrow and spleen) show little differences between fibrotic and non-fibrotic injuries at the first 7 days post injury. Nonetheless, immune cell accumulation at the site of injury, mainly neutrophils at early timepoints, accompanied by an increase in systemic levels of G-CSF, and macrophages at later timepoints is significantly increased in fibrotic group compared to non-fibrotic. Macrophage phenotype is also drastically different between groups. Systemically, splenic macrophages in fibrotic show higher levels of M1 markers compared to non-fibrotic injuries. At the site of injury, fibrotic injuries presented a significantly higher expression of inflammatory markers CD9, CD38 and CXCR4 at earlier timepoints. Fibrotic injuries also presented a significantly lower expression of anti-inflammatory markers CD163 and CD301b. Nanostring analysis on FACS sorted macrophages at Day 3 post injury indicated a general downregulation of most genes in the fibrotic group compared to non-fibrotic. Many of the significantly downregulated genes were part of phagocytic pathways, while the few upregulated genes generally played a role in ECM deposition and adhesion. We have thoroughly characterized immune cell trafficking patterns and macrophage phenotype, systemically and locally, in fibrotic and non-fibrotic injuries. Due to the clear increase in neutrophil presence preceding changes in macrophage phenotype, alongside to high levels of G-CSF systemically and vast literature on neutrophil influence in macrophage phenotype, macrophage-neutrophil interactions will be studied next.
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Details
- Title
- Dysfunctional Macrophage Phenotype in Fibrotic Volumetric Muscle Loss Injury
- Creators
- Ricardo WhitakerKara Spiller
- Publisher
- figshare
- Resource Type
- Conference proceeding
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Other Identifier
- 991021811635504721