Neutrophil-derived MRP-14 is up-regulated in infectious osteomyelitis and stimulates osteoclast generation
Neutrophil-derived MRP-14 is up-regulated in infectious osteomyelitis and stimulates osteoclast generation
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DOI：
10.1189/jlb.3vma1014-482r
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发表时间：
2015-10-01
影响因子：
5.5
通讯作者：
Gaida, Matthias M.
中科院分区：
文献类型：
--
作者：
Dapunt, Ulrike;Giese, Thomas;Gaida, Matthias M.
通过内假体进行关节置换的患者的骨感染（所谓的“假体周围关节感染”）在矫形外科领域中造成严重的问题。诊断通常很困难，在大多数情况下，治疗是复杂和长期的。患者通常需要进行植入物更换手术，因为持续感染和伴随的炎症导致组织损伤和骨降解，从而导致植入物松动。为了深入了解局部炎症过程，评价了促炎细胞因子MRP-14（中性粒细胞的主要成分）的表达及其与随后骨降解的关系。我们发现MRP-14在种植体相关感染患者的受影响组织中显著表达，与趋化因子CXCL 8和中性粒细胞和巨噬细胞的密集浸润密切相关。此外，MRP-14阳性细胞的数量与骨吸收破骨细胞的存在相关。与无菌性炎症患者或健康个体相比，种植体相关感染患者的MRP-14血浆浓度显著更高，提倡MRP-14作为新的诊断标志物。检测到MRP-14的进一步生物活性：rMRP-14直接诱导单核细胞分化为破骨细胞，从而将种植体感染中的炎症反应与破骨细胞生成、骨降解和种植体松动联系起来。
Bone infections of patients with joint replacement by endoprosthesis (so called "periprosthetic joint infection") pose a severe problem in the field of orthopedic surgery. The diagnosis is often difficult, and treatment is, in most cases, complicated and prolonged. Patients often require an implant exchange surgery, as the persistent infection and the accompanying inflammation lead to tissue damage with bone degradation and consequently, to a loosening of the implant. To gain insight into the local inflammatory process, expression of the proinflammatory cytokine MRP-14, a major content of neutrophils, and its link to subsequent bone degradation was evaluated. We found MRP-14 prominently expressed in the affected tissue of patients with implant-associated infection, in close association with the chemokine CXCL8 and a dense infiltrate of neutrophils and macrophages. In addition, the number of MRP-14-positive cells correlated with the presence of bone-resorbing osteoclasts. MRP-14 plasma concentrations were significantly higher in patients with implant-associated infection compared with patients with sterile inflammation or healthy individuals, advocating MRP-14 as a novel diagnostic marker. A further biologic activity of MRP-14 was detected: rMRP-14 directly induced the differentiation of monocytes to osteoclasts, thus linking the inflammatory response in implant infections with osteoclast generation, bone degradation, and implant loosening.