Pharmacokinetics and modeling of immune cell trafficking: quantifying differential influences of target tissues versus lymphocytes in SJL and lipopolysaccharide-treated mice.
Pharmacokinetics and modeling of immune cell trafficking: quantifying differential influences of target tissues versus lymphocytes in SJL and lipopolysaccharide-treated mice.
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DOI：
10.1186/1742-2094-9-231
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发表时间：
2012-10-03
影响因子：
9.3
通讯作者：
Zalcman SS
中科院分区：
文献类型：
--
作者：
Banks WA;Niehoff ML;Ponzio NM;Erickson MA;Zalcman SS
免疫细胞进入中枢神经系统和其他组织在健康和疾病中起着重要作用。快速定量方法是不可用的，可以用来研究免疫细胞-组织相互作用的许多动态方面。我们使用药代动力学和建模来量化和表征放射性标记的淋巴细胞进入脑和外周组织的运输。我们使用2 × 2实验设计的双因素方差分析的方差来模拟淋巴细胞和靶组织在运输中的相对影响。我们发现，在雄性CD-1小鼠中，每克脑中约有1/5，000的静脉注射淋巴细胞进入。在未经处理的SJL雌性动物中，脑摄取量高2至3倍，但脾脏摄取量和血液清除率较低，表明免疫细胞分布存在二分法。用脂多糖（LPS）治疗CD-1小鼠增加了免疫细胞摄取到脑中，但减少了脾脏和腋窝淋巴结的摄取。SJL和CD-1小鼠之间的脑摄取和脾摄取的差异主要由淋巴细胞决定，而LPS摄取的差异主要由脑淋巴细胞决定，但由脾和腋窝淋巴结的组织决定。这些结果表明，免疫细胞通常进入CNS，并且组织和免疫细胞以可以通过药代动力学模型量化的方式相互作用。
Immune cell trafficking into the CNS and other tissues plays important roles in health and disease. Rapid quantitative methods are not available that could be used to study many of the dynamic aspects of immune cell-tissue interactions. We used pharmacokinetics and modeling to quantify and characterize the trafficking of radioactively labeled lymphocytes into brain and peripheral tissues. We used variance from two-way ANOVAs with 2 × 2 experimental designs to model the relative influences of lymphocytes and target tissues in trafficking. We found that in male CD-1 mice, about 1 in 5,000 intravenously injected lymphocytes entered each gram of brain. Uptake by brain was 2 to 3 times higher in naïve SJL females, but uptake by spleen and clearance from blood was lower, demonstrating a dichotomy in immune cell distribution. Treatment of CD-1 mice with lipopolysaccharide (LPS) increased immune cell uptake into brain but decreased uptake by spleen and axillary nodes. Differences in brain uptake and in uptake by spleen between SJL and CD-1 mice were primarily determined by lymphocytes, whereas differences in uptake with LPS were primarily determined by lymphocytes for the brain but by the tissues for the spleen and the axillary lymph node. These results show that immune cells normally enter the CNS and that tissues and immune cells interact in ways that can be quantified by pharmacokinetic models.
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影响因子：
5.4
作者：
Koyanagi, Y;Tanaka, Y;Yamamoto, N
通讯作者：
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影响因子：
100.3
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