In situ macrophage phenotypic transition is affected by altered cellular composition prior to acute sterile muscle injury.

Patsalos, Andreas and Pap, Attila and Varga, T. and Trencsenyi, G. and Garai, I. and Papp, Z. and Dezső, Balázs and Pintye, E. and Nagy, L. (2017) In situ macrophage phenotypic transition is affected by altered cellular composition prior to acute sterile muscle injury. Journal of Physiology, 595 (17). pp. 5815-5842. ISSN 0022-3751, ESSN: 1469-7793

[img] Text
AP VT 2017.pdf - Published Version
Restricted to Registered users only

Download (3MB) | Request a copy


Skeletal muscle regeneration is a complex interplay between various cell types including invading macrophages. Their recruitment to damaged tissues upon acute sterile injuries is necessary for clearance of necrotic debris and for coordination of tissue regeneration. This highly dynamic process is characterized by an in situ transition of infiltrating monocytes from an inflammatory (Ly6Chigh ) to a repair (Ly6Clow ) macrophage phenotype. The importance of the macrophage phenotypic shift and the cross-talk of the local muscle tissue with the infiltrating macrophages during tissue regeneration upon injury are not fully understood and their study lacks adequate methodology. Here, using an acute sterile skeletal muscle injury model combined with irradiation, bone marrow transplantation and in vivo imaging, we show that preserved muscle integrity and cell composition prior to the injury is necessary for the repair macrophage phenotypic transition and subsequently for proper and complete tissue regeneration. Importantly, by using a model of in vivo ablation of PAX7 positive cells, we show that this radiosensitive skeletal muscle progenitor pool contributes to macrophage phenotypic transition following acute sterile muscle injury. In addition, local muscle tissue radioprotection by lead shielding during irradiation preserves normal macrophage transition dynamics and subsequently muscle tissue regeneration. Taken together, our data suggest the existence of a more extensive and reciprocal cross-talk between muscle tissue compartments, including satellite cells, and infiltrating myeloid cells upon tissue damage. These interactions shape the macrophage in situ phenotypic shift, which is indispensable for normal muscle tissue repair dynamics

Item Type: Article
Uncontrolled Keywords: bone marrow transplantation, inflammation, irradiation, macrophage polarization, muscle damage, radioprotection, regeneration, satellite cells
Subjects: Q Science / természettudomány > QP Physiology / élettan
R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában > R850-854 Experimental medicine / kisérleti orvostudomány
Depositing User: Dr Varga Tamás
Date Deposited: 28 Sep 2018 21:08
Last Modified: 28 Sep 2018 21:08

Actions (login required)

Edit Item Edit Item