Targeting Neutrophil Extracellular Traps to Mitigate Post-Traumatic Lower-Extremity Soft Tissue Injury
Abstract
Tissue damage from ischemia reperfusion (IR) injury occurs when blood supply is restored to the tissue following a period of ischemia, such as after a traumatic injury and subsequent repair. A significant source of tissue damage following IR injury is also due to the intense immune system reaction. Here, we target the early immune involvement, specifically neutrophils, to target neutrophil extracellular trap formation to mitigate tissue damage following IR injury. In a mouse model of IR injury, we have investigated multiple PAD4 pathway inhibitors (Cl-Amidine and GDK-199) and found that while these treatments do decrease NET formation in the tissue, a significant reduction in muscle fibrosis was not achieved. However, targeting a different NET-related pathway, TLR9 inhibition, with hydroxychloroquine (Plaquenil(registered trademark)) was shown to decrease IR related skeletal muscle fibrosis and increase muscle regeneration at 5 and 7 days post injury.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1096159
Entities
People
- Benjamin Lévi
Organizations
- University of Michigan