Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis
Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis
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DOI：
10.1073/pnas.1221309110
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发表时间：
2013-08-20
影响因子：
11.1
通讯作者：
Botchwey, Edward
中科院分区：
文献类型：
--
作者：
Awojoodu, Anthony O.;Ogle, Molly E.;Botchwey, Edward
内皮细胞通过产生和分泌血管分泌因子在损伤后的组织调节中起重要作用。至少有两种不同的单核细胞亚群，CD 45（+）CD 11b（+）Gr 1（+）Ly 6C（+）炎症单核细胞和CD 45（+）CD 11b（+）Gr 1（-）Ly 6C（-）抗炎单核细胞，对这些血管分泌因子的反应不同，分别促进病原体/碎片清除和动脉生成/组织再生。我们在此证明，局部1-磷酸鞘氨醇受体3（S1 P（3））激动募集抗炎单核细胞重塑血管。聚（乳酸-羟基乙酸）薄膜用于将FTY 720（一种S1 P（1/3）激动剂）递送至发炎和缺血组织，这导致促炎细胞因子分泌减少和再生细胞因子分泌增加。细胞因子分泌平衡的改变导致从循环中优先募集抗炎单核细胞。这些细胞比炎症单核细胞表达更多的S1 P（3），对SDF-1 α的趋化性也在FTY 720处理后增强，但在S1 P（3）敲除细胞中没有。FTY 720递送增强了小动脉直径扩张并增加了局部脉管系统的长度密度。这项工作确立了S1 P受体信号传导在局部调节组织的血管分泌因子，优先招募再生单核细胞，可以提高愈合结果，组织再生和生物材料植入功能的作用。
Endothelial cells play significant roles in conditioning tissues after injury by the production and secretion of angiocrine factors. At least two distinct subsets of monocytes, CD45(+)CD11b(+)Gr1(+)Ly6C(+) inflammatory and CD45(+)CD11b(+)Gr1(-)Ly6C(-) anti-inflammatory monocytes, respond differentially to these angiocrine factors and promote pathogen/debris clearance and arteriogenesis/tissue regeneration, respectively. We demonstrate here that local sphingosine 1-phosphate receptor 3 (S1P(3)) agonism recruits anti-inflammatory monocytes to remodeling vessels. Poly(lactic-co-glycolic acid) thin films were used to deliver FTY720, an S1P(1/3) agonist, to inflamed and ischemic tissues, which resulted in a reduction in proinflammatory cytokine secretion and an increase in regenerative cytokine secretion. The altered balance of cytokine secretion results in preferential recruitment of anti-inflammatory monocytes from circulation. The chemotaxis of these cells, which expressmore S1P(3) than inflammatory monocytes, toward SDF-1 alpha was also enhanced with FTY720 treatment, but not in S1P(3) knockout cells. FTY720 delivery enhanced arteriolar diameter expansion and increased length density of the local vasculature. This work establishes a role for S1P receptor signaling in the local conditioning of tissues by angiocrine factors that preferentially recruit regenerative monocytes that can enhance healing outcomes, tissue regeneration, and biomaterial implant functionality.