Selective inhibition of the MCP-1-CCR2 ligand-receptor axis decreases systemic trafficking of macrophages in the presence of UHMWPE particles.
Selective inhibition of the MCP-1-CCR2 ligand-receptor axis decreases systemic trafficking of macrophages in the presence of UHMWPE particles.
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DOI：
10.1002/jor.21548
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发表时间：
2012-04
影响因子：
2.8
通讯作者：
Goodman, Stuart B.
中科院分区：
文献类型：
--
作者：
Gibon, Emmanuel;Ma, Ting;Ren, Pei-Gen;Fritton, Kate;Biswal, Sandip;Yao, Zhenyu;Smith, Lane;Goodman, Stuart B.
导致假体周围骨质溶解的生物学机制涉及趋化因子和单核细胞/巨噬细胞系。MCP-1是否在存在磨损颗粒的情况下在巨噬细胞募集中起主要作用尚不清楚。我们测试了两个假设：（1）MCP-1的外源性局部递送诱导系统性巨噬细胞募集和（2）在存在UHMWPE颗粒的情况下，MCP-1配体-受体轴的阻断减少巨噬细胞募集和骨质溶解。使用六组裸鼠。我们使用非侵入性成像来测定巨噬细胞募集和骨质溶解。使用鼠巨噬细胞细胞系和原代野生型和CCR 2敲除鼠巨噬细胞作为报告细胞。将颗粒注入股骨髓腔内。生物发光和免疫组织化学染色用于确认报告细胞的迁移。局部输注MCP-1诱导全身巨噬细胞向骨的运输。注射MCP-1受体拮抗剂可显著减少报告细胞向注入UHMWPE颗粒的骨的募集，并减少骨溶解。当报告细胞缺乏CCR 2受体时，报告细胞向输注颗粒的全身迁移减少。MCP-1配体-受体轴的中断似乎是减轻巨噬细胞运输和UHMWPE颗粒引起的骨质溶解的可行策略。
The biological mechanisms leading to periprosthetic osteolysis involve both chemokines and the monocyte/macrophage cell lineage. Whether MCP-1 plays a major role in macrophage recruitment in the presence of wear particles is unknown. We tested two hypotheses: (1) that exogenous local delivery of MCP-1 induces systematic macrophage recruitment and (2) that blockade of the MCP-1 ligand-receptor axis decreases macrophage recruitment and osteolysis in the presence of UHMWPE particles. Six groups of nude mice were used. We used non-invasive imaging to assay macrophage recruitment and osteolysis. A murine macrophage cell line and primary wild type and CCR2 knockout murine macrophages were used as the reporter cells. Particles were infused into the femoral canal. Bioluminescence and immunohistochemical staining were used to confirm the migration of reporter cells. Locally infused MCP-1 induced systemic macrophage trafficking to bone. Injection of MCP-1 receptor antagonist significantly decreased reporter cell recruitment to bone infused with UHMWPE particles and decreased osteolysis. Systemic migration of reporter cells to infused particles was decreased when the reporter cells were deficient in the CCR2 receptor. Interruption of the MCP-1 ligand-receptor axis appears to be a viable strategy to mitigate trafficking of macrophages and osteolysis due to UHMWPE particles.
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影响因子：
15.3
作者：
Gong, JH;Ratkay, LG;Waterfield, JD;ClarkLewis, I
通讯作者：
ClarkLewis, I
影响因子：
4.1
作者：
Beamer, WG;Donahue, LR;Baylink, DJ
通讯作者：
Baylink, DJ
影响因子：
5.3
作者：
Bozic, Kevin J.;Kurtz, Steven;Berry, Daniel J.
通讯作者：
Berry, Daniel J.
DOI：
10.1097/01.blo.0000149998.88218.05
发表时间：
2005-01-01
影响因子：
4.2
作者：
Goodman, SB;Trindade, M;Smith, RL
通讯作者：
Smith, RL
影响因子：
2.8
作者：
Horowitz, SM;Gonzales, JB
通讯作者：
Gonzales, JB