In situ macrophage phenotypic transition is affected by altered cellular composition prior to acute sterile muscle injury. (8th August 2017)

• Record Type: Journal Article
• Authors: Patsalos, Andreas; Pap, Attila; Varga, Tamas; Trencsenyi, Gyorgy; Contreras, Gerardo Alvarado; Garai, Ildiko; Papp, Zoltan; Dezso, Balazs; Pintye, Eva; Nagy, Laszlo
• Is Part Of: Journal of physiology. Volume 595:Number 17(2017)
• Page Start: 5815
• Page End: 5842
• Publication Date: 2017-08-08
• Subjects: bone marrow transplantation -- inflammation -- irradiation -- macrophage polarization -- muscle damage -- radioprotection -- regeneration -- satellite cells; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP274361
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Myeloid cells play an essential role in skeletal muscle regeneration following acute sterile injury. However, by carrying out bone marrow transplantation we observe delayed muscle regeneration after injury. Radioprotection by lead shielding protects the muscles of mice during gamma irradiation, by preserving the local resident pool of satellite cells that are important for efficient regeneration. The survival of satellite cells and other local populations affects macrophage transition from inflammatory (Ly6C high F4/80 low ) to repair (Ly6C low F4/80 high ) phenotype, which is critical for normal muscle tissue repair dynamics. Abstract : Key points: The in situ phenotypic switch of macrophages is delayed in acute injury following irradiation. The combination of bone marrow transplantation and local muscle radiation protection allows for the identification of a myeloid cell contribution to tissue repair. PET‐MRI allows monitoring of myeloid cell invasion and metabolism. Altered cellular composition prior to acute sterile injury affects the in situ phenotypic transition of invading myeloid cells to repair macrophages. There is reciprocal intercellular communication between local muscle cell compartments, such as PAX7 positive cells, and recruited macrophages during skeletal muscle regeneration. Abstract: 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 (Ly6C high ) to a repair (Ly6C low ) 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.