FIBRIN IS A DETERMINANT OF NEUTROPHIL SEQUESTRATION IN THE LUNG
FIBRIN IS A DETERMINANT OF NEUTROPHIL SEQUESTRATION IN THE LUNG
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DOI：
10.1161/01.res.63.4.735
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发表时间：
1988-10-01
影响因子：
20.1
通讯作者：
MALIK, AB
中科院分区：
文献类型：
--
作者：
COOPER, JA;LO, SK;MALIK, AB
我们研究了纤维蛋白在微栓塞肺部中性粒细胞隔离中的作用。用111in -中性粒细胞和131i -纤维蛋白原对长期制备的清醒绵羊进行肺显像。给予凝血酶（80单位/kg）诱导肺内纤维蛋白隔离。一组给予氨甲环酸（4 mg/kg静脉注射）抑制纤溶，对照组给予生理盐水输注。凝血酶输注使肺中的131i -纤维蛋白原和111in -中性粒细胞均增加，但在纤维蛋白溶解抑制组中，增加幅度更大，持续时间更长。我们检测了分离的中性粒细胞与纤维蛋白基质的粘附性，以研究中性粒细胞与纤维蛋白的相互作用如何介导中性粒细胞的隔离。未刺激的中性粒细胞对纤维蛋白的粘附率为37.5 +/- 3.1%，而对内皮细胞的粘附率为3.9 +/- 0.4%，对琼脂糖的粘附率为6.5 +/- 0.5%。在肉豆蔻酸酯（10(-8)M）活化下，中性粒细胞对纤维蛋白的粘附增加到81.7 +/- 6.2%，并被CD18白细胞粘附糖蛋白β链单克隆抗体抑制。研究结果表明，肺纤维蛋白微血栓的保留与肺嗜中性粒细胞摄取增加有关。纤维蛋白作为中性粒细胞粘附的底物，这种粘附是由中性粒细胞上CD18糖蛋白复合物的表达介导的。肺中纤维蛋白的隔离可能通过诱导肺中性粒细胞摄取而导致肺血管损伤。
We investigated the role of fibrin in the sequestration of neutrophils in lungs challenged with microembolism. Lungs of chronically prepared awake sheep were imaged after infusion of 111In-neutrophils and 131I-fibrinogen. Thrombin (80 units/kg) was administered to induce fibrin sequestration in the lung. One group received tranexamic acid (4 mg/kg i.v.) to inhibit fibrinolysis, and the control group received a saline infusion. Thrombin infusion increased both 131I-fibrinogen and 111In-neutrophils in the lung, but the increases were greater and more prolonged in the fibrinolysis-inhibited group. We examined the adherence of isolated neutrophils to fibrin matrix to investigate how neutrophil-fibrin interactions could mediate neutrophil sequestration. Unstimulated neutrophils showed a 37.5 +/- 3.1% adherence to fibrin in contrast to a 3.9 +/- 0.4% neutrophil adherence to endothelium and a 6.5 +/- 0.5% adherence to agarose. Neutrophil adherence to fibrin increased to 81.7 +/- 6.2% with activation by phorbol myristate acetate (10(-8) M) and was inhibited by a monoclonal antibody directed against the beta-chain of the CD18 leukocyte adhesion glycoprotein. The findings indicate that retention of pulmonary fibrin microthrombi is associated with increased lung uptake of neutrophils. Fibrin serves as a substrate for neutrophil adherence, and this adherence is mediated by expression of the CD18 glycoprotein complex on neutrophils. Fibrin sequestration in the lung may contribute to lung vascular injury by inducing pulmonary neutrophil uptake.