CCL3/CCR1 mediates CD14+CD16- circulating monocyte recruitment in knee osteoarthritis progression
CCL3/CCR1 mediates CD14+CD16- circulating monocyte recruitment in knee osteoarthritis progression
复制标题
CCL3/CCR1 介导膝骨关节炎进展中 CD14 CD16™ 循环单核细胞募集
DOI：
10.1016/j.joca.2020.01.009
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发表时间：
2020-05-01
影响因子：
7
通讯作者：
Meng, F.
中科院分区：
文献类型：
--
作者：
Zhao, X.;Gu, M.;Meng, F.
目的：单核细胞来源的巨噬细胞作为炎症滑膜中增多的主要免疫细胞类型，在膝关节骨关节炎(KOA)的发病过程中发挥着重要作用。然而，骨性关节炎膝关节中循环单核细胞募集的潜在机制仍不确定。方法：采用流式细胞术检测KOA患者和健康志愿者外周血单核细胞表面趋化因子受体CD14(+)、CD16(-)的表达。对膝关节骨性关节炎患者和非膝关节骨性关节炎患者滑液、滑膜和软骨中趋化因子的表达进行了研究。用趋化因子中和抗体(NA)和受体拮抗剂检测趋化因子及其同源受体在CD14(+)、CD16(-)循环单核细胞趋化中的作用。结果：CD14(+)、CD16(-)循环单核细胞多为CCR1-和CCR2-阳性。膝关节骨性关节炎患者滑液中CCL2、CCL3和CCL4水平较正常对照组升高。这些趋化因子最可能的来源是膝关节骨性关节炎的滑膜和软骨发炎。CCL3/CCR1和CCL2/CCR2轴在Transwell实验中表现出强大的募集CD14(+)CD16(-)单核细胞的能力。在胶原酶诱导的膝关节骨性关节炎(CIA)小鼠模型中，阻断CCL3/CCR1轴或CCL2/CCR2轴均可减少滑膜增生和F4/80(+)巨噬细胞的浸润。结论：与CCL2/CCR2轴类似，骨关节炎膝部产生的CCL3可通过CCR1将循环单核细胞趋化到炎症滑膜。(C)2020年国际骨性关节炎研究会。爱思唯尔有限公司出版。保留所有权利。
Objectives: Monocyte-derived macrophages, as the predominant immune cell type that is increased in inflamed synovium, play a vital role during knee osteoarthritis (KOA) progression. However, the mechanisms underlying the recruitment of circulating monocytes to osteoarthritic knees remain uncertain. Based on previous data obtained from plasma, we investigated the contributions of CCL2, CCL3, CCL4 and their cognate receptors in circulating monocyte chemotaxis and KOA development.Methods: Using flow cytometry staining, we characterized the expression patterns of the chemokine receptors in CD14(+)CD16(-) circulating monocytes from KOA patients and healthy volunteers. The expression of chemokines in synovial fluids, synovium and cartilage was investigated in KOA patients and in patients without KOA. The role of chemokines and their cognate receptors in the chemotaxis of CD14(+)CD16(-) circulating monocytes was assessed using chemokine neutralizing antibodies (NA) and receptor antagonists in vitro and in vivo.Results: The majority of CD14(+)CD16(-) circulating monocytes were CCR1-and CCR2- positive. CCL2, CCL3 and CCL4 were elevated in synovial fluid of KOA patients compared with that of controls. The most likely source of these chemokines is inflamed synovium and cartilage in the osteoarthritic knee. The CCL3/CCR1 and CCL2/CCR2 axes showed substantial ability to recruit CD14(+)CD16(-) monocytes in transwell assays. Similar results were confirmed in a mouse model of collagenase-induced KOA (CIA) in which blocking either the CCL3/CCR1 axis or the CCL2/CCR2 axis reduced synovial hyperplasia and F4/80(+) macrophage infiltration.Conclusions: Our findings suggested that, analogous to the CCL2/CCR2 axis, CCL3 produced in osteoarthritic knees can chemoattract circulating monocytes to the inflamed synovium through CCR1. (C) 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.