S1PR5 is pivotal for the homeostasis of patrolling monocytes
S1PR5 is pivotal for the homeostasis of patrolling monocytes
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DOI：
10.1002/eji.201343312
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发表时间：
2013-06-01
影响因子：
5.4
通讯作者：
Walzer, Thierry
中科院分区：
文献类型：
--
作者：
Debien, Emilie;Mayol, Katia;Walzer, Thierry
巡逻Ly 6C（-）单核细胞是血液循环细胞，在炎症和防御病原体中发挥作用。在这里，我们表明，类似于自然杀伤（NK）细胞，巡逻单核细胞表达高水平的S1 PR 5，一个G-偶联受体鞘氨醇-1磷酸。我们发现S1 pr 5（-/-）小鼠缺乏外周Ly 6C（-）单核细胞，但在骨髓（BM）中具有正常数量的这些细胞。各种证据排除了S1 PR 5在外周Ly 6C（-）单核细胞存活中的直接贡献。相反，我们的数据支持S1 PR 5在Ly 6C（-）单核细胞从BM中流出中的作用。特别地，我们观察到S1 PR 5 KO小鼠的BM窦状隙中巡逻单核细胞的频率降低。出乎意料的是，S1 P不是巡逻单核细胞的化学引诱物，并且在体外对其活力没有显著影响。此外，体内S1 P梯度的破坏不会改变Ly 6C（-）单核细胞的运输和活力。这些数据表明，S1 PR 5调节单核细胞的运输通过一种机制，独立于S1 P梯度。
Patrolling Ly6C(-) monocytes are blood-circulating cells that play a role in inflammation and in the defense against pathogens. Here, we show that similar to natural killer (NK) cells, patrolling monocytes express high levels of S1PR5, a G-coupled receptor for sphingosine-1 phosphate. We found that S1pr5(-/-) mice lack peripheral Ly6C(-) monocytes but have a normal number of these cells in the bone marrow (BM). Various lines of evidence exclude a direct contribution of S1PR5 in the survival of Ly6C(-) monocytes at the periphery. Rather, our data support a role for S1PR5 in the egress of Ly6C(-) monocytes from the BM. In particular, we observed a reduced frequency of patrolling monocytes in BM sinusoids of S1PR5 KO mice. Unexpectedly, S1P was not a chemoattractant for patrolling monocytes and had no significant effect on their viability in vitro. Moreover, the disruption of S1P gradients in vivo did not alter Ly6C(-) monocyte trafficking and viability. These data suggest that S1PR5 regulates the trafficking of monocytes via a mechanism independent of S1P gradients.