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Effects of injury size on local and systemic immune cell dynamics in volumetric muscle loss
Preprint   Open access

Effects of injury size on local and systemic immune cell dynamics in volumetric muscle loss

Ricardo Whitaker, Samuel Sung, Tina Tylek, Gregory Risser, Erin O'Brien, Phoebe Ellin Chua, Thomas Li, Ryan J Petrie, Lin Han, Benjamin Binder-Markey, …
bioRxiv
27 Aug 2024
DOI: https://doi.org/10.1101/2024.08.26.609702
PMID: 39253495
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11383310View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

We took a systems approach to the analysis of macrophage phenotype in regenerative and fibrotic volumetric muscle loss outcomes in mice together with analysis of systemic inflammation and of other leukocytes in the muscle, spleen, and bone marrow. Macrophage dysfunction in the fibrotic group occurred as early as day 1, persisted to at least day 28, and was associated with increased numbers of leukocytes in the muscle and bone marrow, increased pro-inflammatory marker expression in splenic macrophages, and changes in the levels of pro-inflammatory cytokines in the blood. The most prominent differences were in muscle neutrophils, which were much more abundant in fibrotic outcomes compared to regenerative outcomes at day 1 after injury. However, neutrophil depletion had little to no effect on macrophage phenotype or on muscle repair outcomes. Together, these results suggest that the entire system of immune cell interactions must be considered to improve muscle repair outcomes.We took a systems approach to the analysis of macrophage phenotype in regenerative and fibrotic volumetric muscle loss outcomes in mice together with analysis of systemic inflammation and of other leukocytes in the muscle, spleen, and bone marrow. Macrophage dysfunction in the fibrotic group occurred as early as day 1, persisted to at least day 28, and was associated with increased numbers of leukocytes in the muscle and bone marrow, increased pro-inflammatory marker expression in splenic macrophages, and changes in the levels of pro-inflammatory cytokines in the blood. The most prominent differences were in muscle neutrophils, which were much more abundant in fibrotic outcomes compared to regenerative outcomes at day 1 after injury. However, neutrophil depletion had little to no effect on macrophage phenotype or on muscle repair outcomes. Together, these results suggest that the entire system of immune cell interactions must be considered to improve muscle repair outcomes.

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