Macrophages in Synovial Inflammation

Abstract

Synovial macrophages are one of the resident cell types in synovial tissue and while they remain relatively quiescent in the healthy joint, they become activated in the inflamed joint and, along with infiltrating monocytes/macrophages, regulate secretion of pro-inflammatory cytokines and enzymes involved in driving the inflammatory response and joint destruction. Synovial macrophages are positioned throughout the sub-lining layer and lining layer at the cartilage–pannus junction and mediate articular destruction. Sub-lining macrophages are now also considered as the most reliable biomarker for disease severity and response to therapy in rheumatoid arthritis (RA). There is a growing understanding of the molecular drivers of inflammation and an appreciation that the resolution of inflammation is an active process rather than a passive return to homeostasis, and this has implications for our understanding of the role of macrophages in inflammation. Macrophage phenotype determines the cytokine secretion profile and tissue destruction capabilities of these cells. Whereas inflammatory synovial macrophages have not yet been classified into one phenotype or another it is widely known that TNFα and IL-l, characteristically released by M1 macrophages, are abundant in RA while IL-10 activity, characteristic of M2 macrophages, is somewhat diminished. Here we will briefly review our current understanding of macrophages and macrophage polarization in RA as well as the elements implicated in controlling polarization, such as cytokines and transcription factors like NFκB, IRFs and NR4A, and pro-resolving factors, such as LXA4 and other lipid mediators which may promote a non-inflammatory, pro-resolving phenotype, and may represent a novel therapeutic paradigm.

Biodegradation of a magnesium alloy implant in the intercondylar femoral notch showed an appropriate response to the synovial membrane in a rabbit model in vivo

“…The obvious hyperplasia of the lining cell layer (4-5 cell layers) in the early postoperative period has been described by other authors. 30 This hyperplasia decreased over the observation period, and a full recovery to physiological conditions was observed after around 30 days. 27,30 In the present study, inflammatory reactions were still present after 30 days, which is consistent with the findings of Nio et al, 29 who induced a post-traumatic synovitis by cutting the ACL.…”

“…30 This hyperplasia decreased over the observation period, and a full recovery to physiological conditions was observed after around 30 days. 27,30 In the present study, inflammatory reactions were still present after 30 days, which is consistent with the findings of Nio et al, 29 who induced a post-traumatic synovitis by cutting the ACL. A study by Huebner et al reported hyperplasia of the lining cell layer and defects in cartilage 9 and 52 weeks after drilling a hole in the femoral notch without using an implant.…”

Proinflammatory M1 Macrophages Inhibit RANKL-Induced Osteoclastogenesis

“…Although the regulation of osteoclastogenesis by macrophages has not previously been reported, macrophages and (pre)osteoclasts can colocalize in the context of inflammatory bone lesion, such as that seen in periodontal disease and arthritis (6,7). While identification of the major macrophage phenotype in human periodontal disease remains elusive (34), we showed that LPS from P. gingivalis, a keystone pathogen in periodontal tissue, can induce M1 macrophages, which suggested that polarization toward the M1 phenotype may occur in periodontal tissue.…”

“…For instance, a recent study (4) revealed that ␥␦-T cells inhibit osteoclastogenesis by their production of interferon gamma (IFN-␥), whereas B and T cells can produce RANKL under inflammatory conditions, thus working toward the promotion of osteoclastogenesis (5). However, in the context of bone lytic diseases involving chronic inflammation, such as periodontitis and rheumatoid arthritis, infiltrations of not only B and T cells but also of macrophages are observed (6,7). It is true that macrophages are the most abundant immune cells found in the synovial membrane in osteoarthritis (8) and in synovial fluid in rheumatoid arthritis (9), outnumbering T and B cells.…”

Xenotransplantation of pig chondrocytes: therapeutic potential and barriers for cartilage repair

“…Synovial macrophages play a major role in the pathogenesis of arthritis (Kennedy et al, 2011). Moreover, monocytes and macrophages are critical effectors in acute xenograft rejection (Li et al, 2009).…”