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Updated: Oct 3, 2026
In Vitro Stimulation and Visualization of Extracellular Trap Release in Differentiated Human Monocyte-derived Macrophages
Published on: November 1, 2019
Effect of mechanical perturbation on the release of PGE(2) by macrophages in vitro
B E Grottkau1, S Noordin, S Shortkroff
1Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
Abstract:
Macrophages play numerous roles in both physiologic and pathologic processes. Along with fibroblasts, they comprise the synovial tissue that forms the lining of musculoskeletal joint capsules and bursae, and they often envelop implants. During the process of phagocytosing prosthesis-related particles, macrophages in peri-implant tissue release inflammatory mediators. Little is known, however, about the response of these cells to mechanical perturbation, which often is a component of the physical environment of the cell. Mouse peritoneal macrophages were grown on a flexible membrane in vitro and a dynamic 1-Hz spatially uniform sinusoidal strain pattern imparted to the elastomeric substrate. The effect of mechanical strain on prostaglandin (PG) E(2) release was evaluated using cells that were activated by lipopolysaccharide (LPS) as well as by those that were not. The results are compared with the levels of PGE(2) stimulated by metallic particles. Strain magnitudes of 4 and 8% applied for 1 h resulted in almost a twofold increase in the release of PGE(2) from LPS-stimulated cells (p < 0.05) and nonstimulated macrophages (p < 0.07), compared with nonperturbated controls. No release was elicited by a challenge of metal particles. These findings demonstrate for the first time an effect of mechanical force on the release of an inflammatory mediator by macrophages. This response may help to explain the macrophage-mediated processes underlying the osteolysis associated with loose prostheses in bone and suggests a mechanism for the inflammation of synovial tissues by excessive mechanical strain.
Insights
Mechanical strain on macrophages significantly increases prostaglandin E(2) release, a key inflammatory mediator. This finding offers new insights into implant loosening and synovial inflammation.
Area of Science:
- Biomedical Engineering
- Immunology
- Cell Biology
Background:
- Macrophages are crucial in physiological and pathological processes, residing in synovial tissues and around implants.
- These cells phagocytose prosthesis particles, releasing inflammatory mediators, but their response to mechanical forces is poorly understood.
Purpose of the Study:
- To investigate the effect of mechanical strain on prostaglandin E(2) release from macrophages.
- To compare the cellular response to mechanical forces versus metallic particles.
Main Methods:
- Mouse peritoneal macrophages were cultured on a flexible membrane and subjected to mechanical strain.
- Prostaglandin E(2) release was measured in both lipopolysaccharide (LPS)-stimulated and nonstimulated cells.
- Results were compared to those stimulated by metallic particles.
Main Results:
- Mechanical strain (4% and 8%) significantly increased prostaglandin E(2) release in both LPS-stimulated and nonstimulated macrophages.
- No prostaglandin E(2) release was observed when cells were challenged with metallic particles.
- This demonstrates a direct effect of mechanical force on inflammatory mediator release by macrophages.
Conclusions:
- Mechanical perturbation of macrophages influences inflammatory mediator release, independent of particle phagocytosis.
- This mechanism may explain macrophage-driven osteolysis in loose prostheses and inflammation in synovial tissues due to excessive mechanical strain.
