Macrophage Activation in the Synovium of Healthy and Osteoarthritic Equine Joints.

Autor: Menarim BC; Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States., Gillis KH; Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States., Oliver A; Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States., Ngo Y; Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States., Werre SR; Laboratory for Study Design and Statistical Analysis, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States., Barrett SH; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States., Rodgerson DH; Hagyard Equine Medical Institute, Lexington, KY, United States., Dahlgren LA; Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Jazyk: angličtina
Zdroj: Frontiers in veterinary science [Front Vet Sci] 2020 Nov 26; Vol. 7, pp. 568756. Date of Electronic Publication: 2020 Nov 26 (Print Publication: 2020).
DOI: 10.3389/fvets.2020.568756
Abstrakt: Synovitis is a major component of osteoarthritis and is driven primarily by macrophages. Synovial macrophages are crucial for joint homeostasis (M2-like phenotype), but induce inflammation (M1-like) when regulatory functions become overwhelmed. Macrophage phenotypes in synovium from osteoarthritic and healthy joints are poorly characterized; however, comparative knowledge of their phenotypes during health and disease is paramount for developing targeted treatments. This study compared patterns of macrophage activation in healthy and osteoarthritic equine synovium and correlated histology with cytokine/chemokine profiles in synovial fluid. Synovial histology and immunohistochemistry for M1-like (CD86), M2-like (CD206, IL-10), and pan macrophage (CD14) markers were performed on biopsies from 29 healthy and 26 osteoarthritic equine joints. Synovial fluid cytokines (MCP-1, IL-10, PGE 2 , IL-1β, IL-6, TNF-α, IL-1ra) and growth factors (GM-CSF, SDF-1α+β, IGF-1, and FGF-2) were quantified. Macrophage phenotypes were not as clearly defined in vivo as they are in vitro . All macrophage markers were expressed with minimal differences between OA and normal joints. Expression for all markers increased proportionate to synovial inflammation, especially CD86. Synovial fluid MCP-1 was higher in osteoarthritic joints while SDF-1 and IL-10 were lower, and PGE 2 concentrations did not differ between groups. Increased CD14/CD86/CD206/IL-10 expression was associated with synovial hyperplasia, consistent with macrophage recruitment and activation in response to injury. Lower synovial fluid IL-10 could suggest that homeostatic mechanisms from synovial macrophages became overwhelmed preventing inflammation resolution, resulting in chronic inflammation and OA. Further investigations into mechanisms of arthritis resolution are warranted. Developing pro-resolving therapies may provide superior results in the treatment of OA.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2020 Menarim, Gillis, Oliver, Ngo, Werre, Barrett, Rodgerson and Dahlgren.)
Databáze: MEDLINE