Urokinase-deficient and urokinase receptor-deficient mice have impaired neutrophil antimicrobial activation in vitro
Urokinase-deficient and urokinase receptor-deficient mice have impaired neutrophil antimicrobial activation in vitro
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DOI：
10.1189/jlb.0104023
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发表时间：
2004-09-01
影响因子：
5.5
通讯作者：
Mayo-Bond, L
中科院分区：
文献类型：
--
作者：
Gyetko, MR;Aizenberg, D;Mayo-Bond, L
白细胞表达尿激酶型纤溶酶原激活物(UPA)和尿激酶受体(uPAR，CD87)。我们已经证明，在铜绿假单胞菌肺炎期间，中性粒细胞在uPAR缺陷(uPAR-/-)小鼠的肺内募集受到损害，但在uPA-/-小鼠中是正常的。然而，与野生型(WT)小鼠相比，uPA-/-小鼠和uPAR-/-小鼠都损害了铜绿假单胞菌的肺清除。为了确定uPA和uPAR在抗菌宿主防御中的作用，我们比较了uPA-/-、uPAR-/-和WT小鼠中性粒细胞的细菌吞噬、呼吸爆发和脱颗粒。中性粒细胞。与WT小鼠相比，uPA-/-和uPAR-/-小鼠的吞噬功能在所有时间点都显著降低。UPA-/-和uPAR-/-中性粒细胞产生的超氧化物大约是WT中性粒细胞的一半。与uPAR-/-或WT-中性粒细胞相比，uPA-/-中性粒细胞中嗜天青颗粒的脱颗粒显著减少。相比之下，与WT相比，激动剂刺激的特定奶奶的释放在uPA-/-或uPAR-/-小鼠中都没有减少。我们得出结论，uPA/uPAR系统调节中性粒细胞激活的几个关键步骤，从而导致细菌杀灭和有效的天然宿主防御。
Leukocytes express both urokinase-type plasminogen activator (uPA) and the urokinase receptor (uPAR, CD87). We have shown that neutrophil recruitment to the lung during P. aeruginosa pneumonia is impaired in uPAR-deficient (uPAR-/-) mice but is normal in uPA-/- mice. However, both uPA-/- mice and uPAR-/- mice have impaired lung clearance of P. aeruginosa compared with wild-type (WT) mice. To determine the role of uPA and uPAR in antibacterial host defense, we compared neutrophil bacterial-phagocytosis, respiratory burst, and degranulation among uPA-/-, uPAR-/-, and WT mice. Neutrophil. phagocytosis was significantly diminished comparing uPA-/- and uPAR-/- mice with WT mice at all time points. The generation of superoxide by both uPA-/- and uPAR-/- neutrophils was about half of that seen in WT neutrophils. Degranulation of azurophilic granules was significantly diminished in uPA-/- neutrophils compared with either uPAR-/- or WT neutrophils. By contrast, agonist-stimulated release of specific grannies was not diminished in either uPA-/- or uPAR-/- mice compared with WT. We conclude that the uPA/uPAR system modulates several of the crucial steps in neutrophil activation that result in bacterial killing and effective innate host defense.