Ontogeny of Synovial Macrophages and the Roles of Synovial Macrophages From Different Origins in Arthritis

Abstract

The ontogeny of macrophages in most organ/tissues in human body has been proven. Due to the limited number and inaccessibility of synovial macrophages (SM), the origin of SM has not been fully illuminated. The objective of this study was designed to investigate the ontogeny of SM and to evaluate the role of SM from different origins in arthritis. Two origins of SM, embryonic SM (ESM) and bone marrow SM (BMSM) were identified in Cx3cr1-EGFP mice, CCR2 −/− mice and bone marrow (BM) chimera model by using a stringent sorting strategy. The cellular features, including dynamic total cell number, in situ proliferation, phagocytosis and expressions of pro-inflammatory and anti-inflammatory genes, of ESM and BMSM were compared. In addition, ESM and BMSM showed different expression patterns in Rheumatoid Arthritis (RA) patients' synovium and during the developmental process of collagen-induced arthritis (CIA) mice. Taken together, these results demonstrated that the SM at least has two origins, ESM and BMSM. The different cellular property and dynamic expression patterns in RA patients/CIA mice highlight the notion that ESM and BMSM might play different role in arthritis.

GRK2 Mediated Abnormal Transduction of PGE2-EP4-cAMP-CREB Signaling Induces the Imbalance of Macrophages Polarization in Collagen-Induced Arthritis Mice

“…However, the role of locally released PGE2 in synovium on macrophage polarization is still not enough to explain. Recently, the origin of synovial macrophages has been revealed by our group [19]. Two types of SM were found: embryonic SMs (ESMs) which were F4/80 + CD11b − and appeared at a mid-embryonic stage; and bone marrow-derived SMs (BMSMs), which were F4/80 − CD11b + and appeared at a late-embryonic stage.…”

“…SMs were plated into DMEM (+5% FBS) containing 1 mg/mL type IV collagenase and incubate for 1.5 h with shaking. After incubation, cells were collected by centrifugation (2500 rpm, 5 min) [19]. RAW macrophages and constructed GRK2 KO macrophages were cultured as previously described [20].…”

“…The flow cytomery was performed according to standard protocol from previous studies [16,19] by using F4/80 (FITC), CD86 (PE) and CD206 (APC). Cells were separated into different tubes and incubated with Cytofix and Cytoperm.…”

“…The membrane expression of EP4 and GRK2 in RAW (M0, M1, M2): The flow cytomery was performed according to standard protocol from previous studies [16,19]. RAWs were separated into different tubes and stained with anti-mouse EP4 antibody (1:100) or anti-mouse GRK2 antibody (1:100) for 1 h. Followed by incubated with anti-mouse Alexa Fluor 488 for 30 min.…”

Synovial Macrophages in Rheumatoid Arthritis: The Past, Present, and Future

“…Previous studies have indicated that the macrophage markers, F4/80 and CD11b, can be used to distinguish embryonic-resident and bone marrow-derived macrophages [28][29][30][31][32][33]. Thus, we attempted to identify embryonic-resident and bone marrow-derived SMs in the synovium [44]. Resident and bone marrow SMs were identified and showed distinct cellular features, including in situ proliferation, phagocytosis, and expression of proinflammatory and anti-inflammatory genes.…”