Participation of the urokinase receptor in neutrophil efferocytosis

Participation of the urokinase receptor in neutrophil efferocytosis
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DOI：
10.1182/blood-2008-12-193524
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发表时间：
2009-07-23
期刊：
BLOOD
影响因子：
20.3
通讯作者：
Abraham, Edward
Abraham, Edward
中科院分区：
医学1区
文献类型：
--
作者：
Park, Young-Jun;Liu, Gang;Abraham, Edward

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尿激酶受体（uPAR）在纤维溶解、细胞迁移和粘附的调节中发挥重要作用。在本研究中，我们检查了 uPAR 是否在调节中性粒细胞胞吞作用中发挥作用。来自uPAR(-/-)小鼠的巨噬细胞在体外和体内的肺中表现出增强吞噬活野生型(WT)中性粒细胞的能力。通过与可溶性uPAR (suPAR)、含精氨酸-甘氨酸-天冬氨酸(RGD) 的肽或抗整合素抗体一起孵育，uPAR(-/-) 巨噬细胞增加的吞噬活性被消除。 WT巨噬细胞对活的uPAR(-/-)中性粒细胞的摄取增加。 uPAR(-/-) 中性粒细胞与 suPAR 或抗整合素抗体一起孵育可将 WT 巨噬细胞的摄取减少至基线。 uPAR(-/-)巨噬细胞对uPAR(-/-)中性粒细胞的摄取没有增强。然而，uPAR(-/-) 中性粒细胞或uPAR(-/-) 巨噬细胞（但不是两者）与suPAR 一起孵育可增强uPAR(-/-) 巨噬细胞对活的uPAR(-/-) 中性粒细胞的摄取。 WT中性粒细胞对uPAR(-/-)巨噬细胞的粘附高于WT巨噬细胞。 uPAR(-/-)中性粒细胞表现出对suPAR的粘附增加，这种粘附可通过阻断低密度脂蛋白相关蛋白和整合素而消除。与存活中性粒细胞上的水平相比，凋亡中性粒细胞表面的uPAR表达降低。这些结果证明了 uPAR 在调节中性粒细胞识别和清除方面的新作用。 （血。2009；114：860-870）
The urokinase receptor (uPAR) plays an important role in regulation of fibronolysis, cell migration, and adhesion. In this study, we examined whether uPAR plays a role in modulating efferocytosis of neutrophils. Macrophages from uPAR(-/-) mice demonstrated enhanced ability to engulf viable wild-type (WT) neutrophils in vitro and in vivo in the lungs. The increased phagocytic activity of uPAR(-/-) macrophages was abrogated by incubation with soluble uPAR (suPAR), arginine-glycine-aspartic acid (RGD)-containing peptides, or anti-integrin antibodies. There was increased uptake of viable uPAR(-/-) neutrophils by WT macrophages. Incubation of uPAR(-/-) neutrophils with suPAR or anti-integrin antibodies diminished uptake by WT macrophages to baseline. Uptake of uPAR(-/-) neutrophils by uPAR(-/-) macrophages was not enhanced. However, incubation of uPAR(-/-) neutrophils or uPAR(-/-) macrophages, but not both, with suPAR enhanced the uptake of viable uPAR(-/-) neutrophils by uPAR(-/-) macrophages. The adhesion of WT neutrophils to uPAR(-/-) macrophages was higher than to WT macrophages. uPAR(-/-) neutrophils demonstrated increased adhesion to suPAR, which was abrogated by blocking of low-density lipoprotein related protein and integrins. Expression of uPAR on the surface of apoptotic neutrophils was reduced compared with levels on viable neutrophils. These results demonstrate a novel role for uPAR in modulating recognition and clearance of neutrophils. (Blood. 2009; 114: 860-870)