Toll-like receptors in the interface membrane around loosening total hip replacement implants
Toll-like receptors in the interface membrane around loosening total hip replacement implants
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DOI：
10.1002/jbm.a.31235
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发表时间：
2007-06-15
影响因子：
4.9
通讯作者：
Salo, Jari
中科院分区：
文献类型：
--
作者：
Takagi, Michiaki;Tamaki, Yasunobu;Salo, Jari
Toll样受体（TLR）是先天免疫的传感器，对微生物和内源性成分的配体有应答。分析异物反应界面膜的典型组织和细胞，以评估TLR在所谓的“全髋关节置换术后无菌性松动”发病机制中的潜在作用。“14例无菌松动全髋关节置换植入物周围的界膜通过单和双免疫组化方法染色，以检查Toll样受体（TLR）-4和TLR-9的细胞定位。骨关节炎滑膜作为对照组织。采用定量逆转录-聚合酶链反应（RT-PCR）检测巨噬细胞TLR-4和TLR-9 mRNA水平。还在培养物中检查了钛颗粒刺激对巨噬细胞的影响。与对照滑膜相比，在异物肉芽肿的滑膜样界膜中观察到TLR-4和TLR-9阳性细胞的广泛免疫定位。TLR和CD 68双重染色显示无菌性松动中TLR阳性细胞主要为单核/巨噬细胞和异物巨细胞。在巨噬细胞集落刺激因子处理的大鼠巨噬细胞中也发现TLR-4和TLR-9 mRNA表达，但在用钛颗粒刺激后，这种表达降低（p < 0.05或更低），尽管用作巨噬细胞活化标志物的基质金属蛋白酶（MMP）-9 mRNA水平增加（p = 0.01）。松动的全髋关节置换植入物周围的界面膜显然配备了TLR，因此可能对微生物的各种结构组分和内源性TLR配体非常敏感。这似乎是由于单核细胞/巨噬细胞的募集，因为颗粒本身似乎下调了一些关键TLR。颗粒吞噬后的这种抑制可以防止过度和有害的宿主反应，以及对无辜旁观者细胞/组织的损伤。(c)2007 Wiley Periodicals，Inc.
Toll-like receptors (TLRs) have been known to act as sensors of innate immunity and respond to ligands of microbial and endogenous components. Tissues and cells typical for interface membrane of foreign body reaction were analyzed to evaluate potential role of TLRs in the pathogenesis of the so called "aseptic loosening of total hip replacement." Fourteen cases of interface membrane around aseptic loose total hip replacement implants were stained by single and double immunohistochemical methods to examine cellular localization of toll-like receptor (TLR)-4 and TLR-9. Osteoarthritic synovium was used as control tissues. Cultured macrophages were used to study TLR-4 and TLR-9 mRNA levels by quantitative reverse transcriptase-polymerase chain reaction. The effect of titanium particle stimulation on macrophages was also examined in the culture. Extensive immunolocalization of TLR-4 and TLR-9 positive cells was observed in the synovial membrane-like interface membrane of foreign body granulomas compared with control synovial membranes. TLR and CD68 double staining demonstrated that the TLR positive cells in aseptic loosening were mostly monocyte/macrophages and foreign body giant cells. TLR-4 and TLR-9 mRNA expression was also found in macrophage-colony stimulating factor treated rat macrophages, but this expression decreased (p < 0.05 or less) upon stimulation with titanium particles although matrix metalloproteinase (MMP)-9 mRNA levels used as macrophage activation marker were increased (p = 0.01). The interface membrane around loosening total hip replacement implants is apparently well equipped with TLRs and, thus, probably very sensitive to various structural components of microbes and to endogenous TLR ligands. This seems to be due to recruitment of monocyte/macrophages as particles per se seemed to down-regulate some of the key TLRs. This suppression after particle phagocytosis might prevent excessive and harmful host responses, and injury to innocent bystander cells/tissues. (c) 2007 Wiley Periodicals, Inc.