The Chemorepellent Slit3 Promotes Monocyte Migration
The Chemorepellent Slit3 Promotes Monocyte Migration
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DOI：
10.4049/jimmunol.0903898
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发表时间：
2010-12-15
影响因子：
4.4
通讯作者：
van Hennik, Paula B.
中科院分区：
文献类型：
--
作者：
Geutskens, Sacha B.;Hordijk, Peter L.;van Hennik, Paula B.
定向迁移是单核细胞浸润炎症部位的重要步骤，这一过程主要由化学引诱物调节。狭缝是由内皮细胞分泌的大基质蛋白;据报道，它们抑制化学引诱剂诱导的不同细胞类型（包括白细胞）的迁移。本研究的目的是确定Slit 3对初级单核细胞迁移的影响，并解决潜在的机制。我们发现，Roundabout（Robo）1是识别Slit 3的Robo受体之一，是CD 14（+）单核细胞表达的唯一Robo同系物。有趣的是，我们发现用Slit 3刺激增加了体外原代单核细胞的自发和趋化因子诱导的迁移，并增加了体内腹膜炎症期间的髓样细胞募集。此外，Slit 3本身似乎并不充当化学引诱物;它通过诱导化学动力学效应来促进由化学引诱物（如CXCL 12）触发的定向迁移。我们进一步表明，Slit 3阻止单核细胞扩散，并诱导扩散的单核细胞变圆，而不影响单核细胞粘附。Slit 3的刺激与磷酸化p38、p42/p44或Src（已知的单核细胞迁移调节因子）水平的变化无关，但它通过激活RhoA直接作用于参与基础白细胞迁移的分子途径。这些发现表明单核细胞对Slit 3的意外反应，并增加了对Slit蛋白在炎症细胞募集过程中可能作用的见解。免疫学杂志，2010，185：7691-7698。
Directional migration is an essential step for monocytes to infiltrate sites of inflammation, a process primarily regulated by chemoattractants. Slits are large matrix proteins that are secreted by endothelial cells; they were reported to inhibit the chemoattractant-induced migration of different cell types, including leukocytes. The aim of this study was to determine the effect of Slit3 on primary monocyte migration and to address the underlying mechanisms. We show that Roundabout (Robo) 1, one of the Robo receptors that recognize Slit3, is the only Robo homolog expressed by CD14(+) monocytes. Interestingly, we found that stimulation with Slit3 increased the spontaneous and chemoattractant-induced migration of primary monocytes in vitro and increased the myeloid cell recruitment during peritoneal inflammation in vivo. In addition, Slit3 did not seem to act as a chemoattractant itself; it promoted directed migration triggered by chemoattractants, such as CXCL12, by inducing a chemokinetic effect. We further show that Slit3 prevented monocyte spreading and induced rounding of spread monocytes without affecting monocyte adhesion. Stimulation with Slit3 was not associated with changes in the levels of phosphorylated p38, p42/p44, or Src, known regulators of monocyte migration, but it directly acts on molecular pathways involved in basal leukocyte migration by activating RhoA. These findings show an unexpected response of monocytes to Slit3 and add insights into the possible role of Slit proteins during inflammatory cell recruitment. The Journal of Immunology, 2010, 185: 7691-7698.