title: Anti-inflammatory macrophages improve skeletal muscle recovery from ischemia-reperfusion.
abstract: The presence of macrophages (MPs) is essential for skeletal muscle to properly regenerate following injury. The aim of this study was the evaluation of MP profiles and their importance in skeletal muscle recovering from tourniquet-induced ischemia-reperfusion (I/R). Using flow cytometry, we identified two distinct CD11b(+) MP populations that differ in expression of the surface markers Ly-6C and F4/80. These populations are prominent at 3 and 5 days of reperfusion and molecularly correspond to inflammatory and anti-inflammatory MP phenotypes. Sorted MP populations demonstrated high levels of IGF-I expression, and whole muscle post-I/R IGF-I expression strongly correlates with F4/80 expression. This suggests MPs largely influence postinjury IGF-I upregulation. We additionally demonstrate that direct intramuscular injection of FACS-isolated CD11b(+)Ly-6C(lo)F4/80(hi) MPs improves the functional and histological recovery of I/R-affected muscle. Taken together, these data further support the substantial influence of the innate immune system on muscle regeneration and suggest MP-focused therapeutic approaches may greatly facilitate skeletal muscle recovery from substantial injury.
authors: Department of Kinesiology, The University of Texas at Austin, Austin, Texas; and.
authors: David W
authors: DW
authors: Hammers
authors: Department of Kinesiology, The University of Texas at Austin, Austin, Texas; and.
authors: Viktoriya
authors: V
authors: Rybalko
authors: Department of Kinesiology, The University of Texas at Austin, Austin, Texas; and.
authors: Melissa
authors: M
authors: Merscham-Banda
authors: Department of Kinesiology, The University of Texas at Austin, Austin, Texas; and.
authors: Pei-Ling
authors: PL
authors: Hsieh
authors: Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas.
authors: Laura J
authors: LJ
authors: Suggs
authors: Department of Kinesiology, The University of Texas at Austin, Austin, Texas; and rfarrar@austin.utexas.edu.
authors: Roger P
authors: RP
authors: Farrar
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply / Q000293:injuries*; D020127:Recovery of Function / Q000276:immunology*; D015427:Reperfusion Injury / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; C494192:Ly-6C antigen, mouse
keywords: flow cytometry; macrophage; myogenesis; regenerative medicine; reperfusion