P-selectin glycoprotein ligand-1 regulates adhesive properties of the endothelium and leukocyte trafficking into adipose tissue.
P-selectin glycoprotein ligand-1 regulates adhesive properties of the endothelium and leukocyte trafficking into adipose tissue.
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DOI：
10.1161/circresaha.110.218651
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发表时间：
2010-08-06
影响因子：
20.1
通讯作者：
Eitzman DT
中科院分区：
文献类型：
--
作者：
Russo HM;Wickenheiser KJ;Luo W;Ohman MK;Franchi L;Wright AP;Bodary PF;Núñez G;Eitzman DT
内皮细胞和白细胞之间的粘附相互作用影响脂肪组织中白细胞的运输。p -选择素糖蛋白配体-1 （Psgl-1）在这一过程中的作用尚不清楚。本研究的目的是确定Psgl-1缺乏对内皮细胞粘附特性和白细胞聚集到肥胖脂肪库的影响。建立肥胖遗传模型，研究Psgl-1缺乏对白细胞运输的影响。与瘦小鼠（Lepr +/+,Psgl-1+/+）相比，肥胖瘦素受体突变小鼠（Lepr db/db,Psgl-1+/+）的白细胞内皮相互作用增加，但肥胖、Psgl-1缺陷小鼠（Lepr db/db,Psgl-1−/−）的白细胞内皮相互作用没有增加。这种Psgl-1缺乏的影响是由于Psgl-1的间接作用，因为Psgl-1+/+过继转移的白细胞在Lepr db/db、Psgl-1−/−小鼠中没有表现出增强的滚动。此外，与Leprdb/db、Psgl-1+/+小鼠相比，Leprdb/db、Psgl-1−/−小鼠的循环p -选择素、e -选择素、单核细胞化学引诱蛋白-1水平和内脏脂肪组织巨噬细胞含量降低。在饮食诱导的肥胖小鼠模型中也观察到，由于Psgl-1缺乏，白细胞内皮相互作用和内脏脂肪组织巨噬细胞含量减少。Psgl-1−/−小鼠对外源性IL-1β的内皮作用有抵抗力，这表明细胞因子信号传导缺陷导致Psgl-1缺乏对白细胞-内皮相互作用的影响。IL-1受体缺乏的小鼠循环p -选择素水平也降低，与Psgl-1−/−小鼠相似。Psgl-1的缺乏与IL-1受体介导的内皮粘附特性降低有关，并对肥胖小鼠的内脏脂肪炎症具有保护作用。
Adhesive interactions between endothelial cells and leukocytes affect leukocyte trafficking in adipose tissue. The role of P-selectin glycoprotein ligand-1 (Psgl-1) in this process is unclear. The goal of this study was to determine the effect of Psgl-1 deficiency on adhesive properties of the endothelium and on leukocyte recruitment into obese adipose depots. A genetic model of obesity was generated to study the effects of Psgl-1 deficiency on leukocyte trafficking. Leukocyte-endothelial interactions were increased in obese leptin receptor mutant mice (Lepr db/db,Psgl-1+/+), but not obese, Psgl-1 deficient mice (Lepr db/db,Psgl-1−/−), when compared to lean mice (Lepr +/+,Psgl-1+/+). This effect of Psgl-1 deficiency was due to indirect effects of Psgl-1, since Psgl-1+/+ adoptively transferred leukocytes did not exhibit enhanced rolling in Lepr db/db,Psgl-1−/− mice. Additionally, circulating levels of P-selectin, E-selectin, Monocyte chemoattractant protein-1, and macrophage content of visceral adipose tissue were reduced in Leprdb/db,Psgl-1−/− compared to Leprdb/db,Psgl-1+/+ mice. Reduced leukocyte-endothelial interactions and macrophage content of visceral adipose tissue due to Psgl-1 deficiency was also observed in a diet-induced obese mouse model. Psgl-1−/− mice were resistant to the endothelial effects of exogenous IL-1β, suggesting that defective cytokine signaling contributes to the effect of Psgl-1 deficiency on leukocyte-endothelial interactions. Mice deficient in the IL-1 receptor also had reduced levels of circulating P-selectin, similar to those observed in Psgl-1−/− mice. Deficiency of Psgl-1 is associated with reduced IL-1 receptor-mediated adhesive properties of the endothelium and is protective against visceral fat inflammation in obese mice.