Effect of mechanical perturbation on the release of PGE(2) by macrophages in vitro

Macrophages play numerous roles in both physiologic and pathologic processe s. Along with fibroblasts, they comprise the synovial tissue that forms the lining of musculoskeletal joint capsules and bursae, and they often envelo p implants. During the process of phagocytosing prosthesis-related particle s, macrophages in peri-implant tissue release inflammatory mediators. Littl e is known, however, about the response of these cells to mechanical pertur bation, which often is a component of the physical environment of the cell. Mouse peritoneal macrophages were grown on a flexible membrane bi vitro an d a dynamic 1-Hz spatially uniform sinusoidal strain pattern imparted to th e elastomeric substrate. The effect of mechanical strain on prostaglandin ( PG) E-2 release was evaluated using cells that were activated by lipopolysa ccharide (LPS) as well as by those that were not. The results are compared with the levels of PGE(2) stimulated by metallic particles. Strain magnitud es 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 m acrophages (p < 0.07), compared with nonperturbated controls. No release wa s elicited by a challenge of metal particles. These findings demonstrate fo r the first time an effect of mechanical force on the release of an inflamm atory mediator by macrophages. This response may help to explain the macrop hage-mediated processes underlying the osteolysis associated with loose pro stheses in bone and suggests a mechanism for the inflammation of CIO synovi al tissues by excessive mechanical strain. (C) 2001 John Wiley & Sons, Inc.