Photodynamic therapy using intra-articular Photofrin for murine MRSA arthritis: biphasic light dose response for neutrophil-mediated antibacterial effect.
Photodynamic therapy using intra-articular Photofrin for murine MRSA arthritis: biphasic light dose response for neutrophil-mediated antibacterial effect.
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DOI：
10.1002/lsm.21037
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发表时间：
2011-03
影响因子：
2.4
通讯作者：
Morimoto, Yuji
中科院分区：
文献类型：
--
作者：
Tanaka, Masamitsu;Kinoshita, Manabu;Yoshihara, Yasuo;Shinomiya, Nariyoshi;Seki, Shuhji;Nemoto, Koichi;Hamblin, Michael R.;Morimoto, Yuji
关键词：
细菌性关节炎对抗生素反应不佳，而且多重耐药性正在蔓延。我们之前在耐甲氧西林金黄色葡萄球菌（MRSA）关节炎的小鼠模型中测试了全身性Photofrin®介导的光动力疗法（PDT），但发现中性粒细胞被PDT杀死，因此感染增强。本研究采用关节内注射Photofrin®，并优化了光剂量测定法，以最大限度地杀灭细菌，并最大限度地减少对宿主中性粒细胞的杀灭。将MRSA（5 × 107 CFU）注射到小鼠膝关节中，3天后在5分钟内用1 μg Photofrin®和635-nm二极管激光照射（一系列能量密度）。在PDT后6小时或1-3、5和7天采集滑液，以确定MRSA菌落形成单位（CFU）、中性粒细胞数量和细胞因子水平。观察到双相光剂量反应，其中在20 J cm−2的通量下观察到MRSA CFU的最大减少，而在更低或更高的通量下观察到较低的抗菌功效。与这些结果一致，与5或70 J cm−2的能量密度相比，20 J cm −2的能量密度的PDT后，在感染的膝关节中观察到巨噬细胞炎性蛋白-2（CXC趋化因子）的浓度显著更高，中性粒细胞的积聚更大。用于小鼠MRSA关节炎的PDT需要适当的光剂量测定，以同时最大限度地杀死细菌和中性粒细胞积聚到感染部位，而太少的光不能杀死足够的细菌，而太多的光会杀死中性粒细胞并损害宿主组织和细菌，并允许细菌通过宿主防御不受阻碍地生长。
Bacterial arthritis does not respond well to antibiotics and moreover multidrug resistance is spreading. We previously tested photodynamic therapy (PDT) mediated by systemic Photofrin® in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) arthritis, but found that neutrophils were killed by PDT and therefore the infection was potentiated. The present study used an intra-articular injection of Photofrin® and optimized the light dosimetry in order to maximize bacterial killing and minimize killing of host neutrophils. MRSA (5 × 107 CFU) was injected into the mouse knee followed 3 days later by 1 μg of Photofrin® and 635-nm diode laser illumination with a range of fluences within 5 minutes. Synovial fluid was sampled 6 hours or 1–3, 5, and 7 days after PDT to determine MRSA colony-forming units (CFU), neutrophil numbers, and levels of cytokines. A biphasic light dose response was observed with the greatest reduction of MRSA CFU seen with a fluence of 20 J cm−2, whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. Consistent with these results, a significantly higher concentration of macrophage inflammatory protein-2, a CXC chemokine, and greater accumulation of neutrophils were seen in the infected knee joint after PDT with a fluence of 20 J cm−2 compared to fluences of 5 or 70 J cm−2. PDT for murine MRSA arthritis requires appropriate light dosimetry to simultaneously maximize bacterial killing and neutrophil accumulation into the infected site, while too little light does not kill sufficient bacteria and too much light kills neutrophils and damages host tissue as well as bacteria and allows bacteria to grow unimpeded by host defense.
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影响因子：
3.4
作者：
Torikai, Eiji;Kageyama, Yasunori;Nagano, Akira
通讯作者：
Nagano, Akira
影响因子：
3.3
作者：
Tanaka, Masamitsu;Kinoshita, Manabu;Morimoto, Yuji
通讯作者：
Morimoto, Yuji
影响因子：
3.1
作者：
Bisland, SK;Chien, C;Burch, S
通讯作者：
Burch, S
影响因子：
3.1
作者：
Gad, F;Zahra, T;Hamblin, MR
通讯作者：
Hamblin, MR
DOI：
10.1155/dte.5.175
发表时间：
1999
期刊：
Diagnostic and therapeutic endoscopy
影响因子：
--
作者：
Mimura S;Narahara H;Otani T;Okuda S
通讯作者：
Okuda S