TISSUE DISTRIBUTION AND CLEARANCE OF SOLUBLE MURINE TNF RECEPTORS IN MICE
TISSUE DISTRIBUTION AND CLEARANCE OF SOLUBLE MURINE TNF RECEPTORS IN MICE
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DOI：
10.1016/1043-4666(94)90048-5
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发表时间：
1994-11-01
期刊：
影响因子：
3.8
通讯作者：
BUURMAN, WA
中科院分区：
文献类型：
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作者：
BEMELMANS, MHA;GOUMA, DJ;BUURMAN, WA
在本研究中，研究了sTNFR的清除。数据显示，双侧肾切除术导致两种sTNFR水平的增加，之后发展出新的稳态情况，表明除肾脏外的其他器官参与sTNFR的清除。双侧肾切除术也导致循环TNF的增加。这种TNF通过ELISA检测，似乎没有生物活性。为了研究内毒素诱导的sTNFR增加是否依赖于肾功能，将内毒素注射到肾切除小鼠中。数据显示，肾切除术后注射内毒素导致两种sTNFR水平的进一步增加。然而，在肾切除小鼠中内毒素诱导的增加与LPS后正常小鼠中的情况相似，表明在这些小鼠中内毒素诱导的增加是肾脏非依赖性的。为了研究各种器官在sTNFR清除中的相对参与，注射I-125标记的sTNFR-P75。数据显示，大部分sTNFR通过肾脏从循环中去除，尽管也获得了肝脏和肺受累的指征。参数清除率的计算显示，肾切除导致sTNFR-P75清除率降低50%。此外，所呈现的数据强烈表明，sTNFR释放似乎是一个连续的过程，其与肾脏对sTNFR的清除保持平衡，尽管涉及其他器官如肝和肺。
In this study, clearance of sTNFR was investigated. The data show that bilateral nephrectomy results in an increase of the levels of both sTNFR after which a new steady state situation develops, suggesting that other organs, apart from the kidneys, are involved in clearing of sTNFR. Bilateral nephrectomy also leads to an increase in circulating TNF. This TNF was detected by ELISA and appeared to be not biologically active. To investigate whether the endotoxin induced increase in sTNFR is dependent of renal function, endotoxin was injected in nephrectomized mice. The data show that nephrectomy followed by endotoxin injection resulted in a further increase of the levels of both sTNFR. However, the endotoxin induced increase in nephrectomized mice was similar to the situation in normal mice after LPS indicating that the endotoxin induced increase is kidney independent in these mice. To investigate the relative participation of various organs in sTNFR clearance, I-125 labelled sTNFR-P75 was injected. The data reveal that the majority of the sTNFR is removed from the circulation by the kidneys although indications for involvement of the liver and the lungs were also obtained. Calculation of the parametric clearance revealed that nephrectomy resulted in a 50% reduction of sTNFR-P75 clearance. Furthermore, the data presented strongly suggest that sTNFR release seems to be a continuous process, which is in balance with clearance of the sTNFR by the kidney, although other organs such as the liver and the lungs are involved.