title: Effect of mechanical perturbation on the release of PGE(2) by macrophages in vitro.
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.
authors.affiliation: Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Grottkau
authors.forename: S
authors.initials: S
authors.lastname: Noordin
authors.forename: S
authors.initials: S
authors.lastname: Shortkroff
authors.forename: J L
authors.initials: JL
authors.lastname: Schaffer
authors.forename: T S
authors.initials: TS
authors.lastname: Thornhill
authors.forename: M
authors.initials: M
authors.lastname: Spector
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010014:Osteolysis / Q000209:etiology / Q000503:physiopathology; D010587:Phagocytosis; D011475:Prosthesis Failure; D013314:Stress, Mechanical
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D015232:Dinoprostone