The chemokine receptors CCR2 and CX3CR1 mediate monocyte/macrophage trafficking in kidney ischemia-reperfusion injury.
The chemokine receptors CCR2 and CX3CR1 mediate monocyte/macrophage trafficking in kidney ischemia-reperfusion injury.
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DOI：
10.1038/ki.2008.500
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发表时间：
2008-12
影响因子：
19.6
通讯作者：
Okusa, Mark D.
中科院分区：
文献类型：
--
作者：
Li, Li;Huang, Liping;Sung, Sun-Sang J.;Vergis, Amy L.;Rosin, Diane L.;Rose, C. Edward, Jr.;Lobo, Peter I.;Okusa, Mark D.
趋化因子及其受体如CCR 2和CX 3CR 1介导白细胞粘附和迁移到损伤组织中。为了进一步确定肾损伤过程中单核细胞运输的机制，我们在正常小鼠肾脏中鉴定了两组F4/80阳性细胞（F4/80低和F4/80高），其表型分别对应于巨噬细胞和树突状细胞。缺血再灌注3小时后，大量F4/80低炎症单核细胞（而非树突状细胞）流入肾脏。这些单核细胞产生TNF-α、IL-6、IL-1 α和IL-12。与对照小鼠相比，在CCR 2 −/−小鼠或CCR 2 +/+小鼠中诱导的缺血性损伤（与CCR 2 −/−骨髓嵌合）导致血浆肌酐水平降低，肾脏中浸润的F4/80 low巨噬细胞减少。CX 3CR 1表达有助于单核细胞募集到发炎的肾脏，因为CX 3CR 1 −/−小鼠的缺血性损伤减少，F4/80低巨噬细胞比对照组少。从CCR 2 +/+或CX 3CR 1 +/−小鼠转移的单核细胞比从CCR 2 −/−或CX 3CR 1 −/−小鼠转移的单核细胞更好地迁移到再灌注肾中。从CCR 2 +/+小鼠（而不是CCR 2 −/−小鼠）连续转移单核细胞，逆转了缺血再灌注后CCR 2 −/−小鼠的保护作用。CD 11b + Ly 6Chigh单核细胞从血液进入发炎的肾脏是CCR 2和CX 3CR 1依赖性的。我们的研究表明，炎症单核细胞迁移，通过CCR 2和CX 3CR 1依赖的机制，在缺血再灌注后的肾损伤中起着关键作用。
Chemokines and their receptors such as CCR2 and CX3CR1 mediate leukocyte adhesion and migration into injured tissue. To further define mechanisms of monocyte trafficking during kidney injury we identified two groups of F4/80-positive cells (F4/80low and F4/80high) in the normal mouse kidney that phenotypically correspond to macrophages and dendritic cells, respectively. Following ischemia and 3 h of reperfusion, there was a large influx of F4/80low inflamed monocytes, but not dendritic cells, into the kidney. These monocytes produced TNF-α, IL-6, IL-1 α and IL-12. Ischemic injury induced in CCR2−/− mice or in CCR2+/+ mice, made chimeric with CCR2−/− bone marrow, resulted in lower plasma creatinine levels and their kidneys had fewer infiltrated F4/80low macrophages compared to control mice. CX3CR1 expression contributed to monocyte recruitment into inflamed kidneys, as ischemic injury in CX3CR1−/− mice was reduced, with fewer F4/80low macrophages than controls. Monocytes transferred from CCR2+/+ or CX3CR1+/− mice migrated into reperfused kidneys better than monocytes from either CCR2−/− or CX3CR1−/− mice. Adoptive transfer of monocytes from CCR2+/+ mice, but not CCR2−/− mice, reversed the protective effect in CCR2−/− mice following ischemia-reperfusion. Egress of CD11b+Ly6Chigh monocytes from blood into inflamed kidneys was CCR2- and CX3CR1-dependent. Our study shows that inflamed monocyte migration, through CCR2- and CX3CR1-dependent mechanisms, plays a critical role in kidney injury following ischemia reperfusion.
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影响因子：
37.8
作者：
Combadière, C;Potteaux, S;Mallat, Z
通讯作者：
Mallat, Z
影响因子：
19.6
作者：
Dong, X.;Swaminathan, S.;Griffin, M. D.
通讯作者：
Griffin, M. D.
影响因子：
6.1
作者：
Jo, SK;Sung, SA;Kim, HK
通讯作者：
Kim, HK
DOI：
10.1152/ajprenal.00378.2004
发表时间：
2005-04-01
影响因子：
4.2
作者：
Day, YJ;Huang, L;Okusa, MD
通讯作者：
Okusa, MD
DOI：
10.1097/01.asn.0000089563.63641.a8
发表时间：
2003-10-01
影响因子：
13.6
作者：
Furuichi, K;Wada, T;Yokoyama, H
通讯作者：
Yokoyama, H