Tissue-specific mechanisms control the retention of IL-8 in lungs and skin
Tissue-specific mechanisms control the retention of IL-8 in lungs and skin
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DOI：
10.4049/jimmunol.168.7.3550
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发表时间：
2002-04-01
影响因子：
4.4
通讯作者：
Martin, TR
中科院分区：
文献类型：
--
作者：
Frevert, CW;Goodman, RB;Martin, TR
趋化因子是一组结构上相关的肽，其促进组织中白细胞的定向迁移。控制组织中趋化因子保留的机制还不清楚。在这项研究中，我们提出的证据表明，两种不同的机制控制的持久性CXC趋化因子，IL-8，在肺和皮肤。将I-125-标记的IL-8注射到肺的气隙和皮肤的真皮中，并通过闪烁计数测量在特定时间残留的I-125-标记的IL-8的量。I-125标记的IL-8从皮肤中清除的速度比从肺中清除的速度快得多，因为在4 h时只有2%的I-125标记的IL-8保留在皮肤中，而在4 h时有50%的I-125标记的IL-8保留在肺中。在血小板减少的家兔中的研究表明，中性粒细胞缩短了I-125标记的IL-8在皮肤中的滞留，但对肺没有影响。IL-8的单体形式，N-甲基-亮氨酸25 IL-8，在肺中的保留时间不如重组人IL-8长，表明IL-8的二聚化是增加局部浓度并阻止I-125标记的IL-8在肺中保留的机制。这些观察结果表明，控制IL-8在组织中的保留的机制包括中性粒细胞迁移和二聚化，并且这些的重要性在不同组织中不同。
Chemokines are a group of structurally related peptides that promote the directed migration of leukocytes in tissue. Mechanisms controlling the retention of chemokines in tissue are not well understood. In this study we present evidence that two different mechanisms control the persistence of the CXC chemokine, IL-8, in lungs and skin. I-125-labeled IL-8 was Injected into the airspaces of the lungs and the dermis of the skin and the amount of I-125-labeled IL-8 that remained at specified times was measured by scintillation counting. The I-125-labeled IL-8 was cleared much more rapidly from skin than lungs, as only 2% of the I-125-labeled IL-8 remained in skin at 4 h whereas 50% of the I-125-labeled IL-8 remained in lungs at 4 h. Studies in neutropenic rabbits showed that neutrophils shortened the retention of I-125-labeled IL-8 in skin but not lungs. A monomeric form of IL-8, N-methyl-leucine 25 IL-8, was not retained as long in lungs as recombinant human IL-8, indicating that dimerization of IL-8 is a mechanism that increases the local concentration and prolongs the retention of I-125-labeled IL-8 in lungs. These observations show that the mechanisms that control the retention of IL-8 in tissue include neutrophil migration and dimerization, and that the importance of these varies in different tissues.