M1 and M2 Macrophage Polarization in vitro with exposure to LPS and IL-4

摘要

Replacement of arthritic joints with artificial materials is a frequently performed surgical procedure. The articulating surfaces wear with usage generating particulate debris, which is usually processed and phagocytosed by monocyte/macrophages leading to their proliferation and activation. Once activated, macrophages produce pro-inflammatory cytokines leading to periprosthetic bone loss, or osteolysis. A current hypothesis suggests that macrophage activation in osteolysis may be polarized. Ml macrophages may promote an inflammatory response early with production of mediators such as IL-1, IL-6, IL-8, MMPs, and TNF-α. In contrast, M2 macrophages may act later in an anti-inflammatory response to promote bone healing, debris scavenging, wound healing, and angiogenesis by utilizing mediators such as IL-4, IL-10, and IL-13. In this study, we investigate the differential expression of M1 and M2 murine macrophages when stimulated by lipopolysaccharide (LPS). The use of LPS simulates endotoxin, which has been reported to be present on some revised implants and byproducts of wear of joint replacements, possibly contributing to periprosthetic osteolysis. Our hypothesis is that there is a higher ratio of M1/M2 macrophages in response to activation with LPS, and that the administration of IL-4 can drive these M1 macrophages to M2 macrophages in vitro.