Differential transport of rat and human interleukin-1α across the blood–brain barrier and blood–testis barrier in rats

Differential transport of rat and human interleukin-1α across the blood–brain barrier and blood–testis barrier in rats
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大鼠和人白细胞介素 1α 穿过大鼠血脑屏障和血睾屏障的差异转运

DOI:
10.1016/s0006-8993(00)02772-4
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发表时间:
2000
期刊:
影响因子:
2.9
通讯作者:
A. Kastin
A. Kastin
中科院分区:
医学3区
文献类型:
--
作者:
S. Plotkin;W. Banks;L. Maness;A. Kastin

文献摘要

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人白细胞介素-1α通过饱和转运系统通过小鼠血脑屏障(BBB)和血睾丸屏障(BTB)进行转运。人类IL-1在小鼠和大鼠脑中的生物活性和结合的差异,提高了IL-1在血脑屏障和BTB之间运输的物种差异的可能性。我们利用灵敏的体内技术和膜放射自显影技术测量了重组人125i - il -1α (I-huIL-1α)和鼠125i - il -1α (I-ratIL-1α)在大鼠血脑屏障和BTB静脉注射后的转运。I-ratIL-1α在大鼠血脑屏障和大鼠BTB中的穿过率与先前报道的小鼠IL-1α在小鼠中的穿过率相当。通过添加未标记的大鼠IL-1α抑制血脑屏障的通道,显示饱和运输。相比之下,I-huIL-1α进入大鼠大脑的速度要慢得多,并且不受添加未标记的人IL-1α的抑制。这些结果表明,大鼠白细胞介素-1转运体不像小鼠转运体那样转运人IL-1α。这一差异突出了物种特异性在IL-1α转运中的重要性,并可能部分解释了啮齿动物对外源性人IL-1α的不同生理反应。
Human interleukin-1α is transported across the murine blood–brain barrier (BBB) and blood–testis barrier (BTB) by a saturable transport system. Differences in the biological activity and binding of human IL-1 in mouse and rat brain raise the possibility of species differences in the transport of IL-1 across the BBB and BTB. We measured the transport of recombinant human125I-IL-1α (I-huIL-1α) and rat125I-IL-1α (I-ratIL-1α) across the rat BBB and BTB after intravenous injection using a sensitive in vivo technique and film autoradiography. I-ratIL-1α was found to cross the rat BBB and rat BTB at rates comparable to those reported previously for murine IL-1α in mice. Passage across the BBB was inhibited by the addition of unlabeled rat IL-1α, demonstrating saturable transport. In contrast, I-huIL-1α entered the brain of the rat much more slowly, and its entry was not inhibited by the addition of unlabeled human IL-1α. These results show that the rat interleukin-1 transporter, unlike the murine transporter, does not transport human IL-1α. This difference highlights the importance of species specificity in IL-1α transport and may partly explain the different physiological responses to exogenous human IL-1α among rodent species.