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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Increased PSGL-1 expression on granulocytes from allergic-asthmatic subjects results in enhanced leukocyte recruitment under flow conditions.
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Increased PSGL-1 expression on granulocytes from allergic-asthmatic subjects results in enhanced leukocyte recruitment under flow conditions.

机译:来自过敏性哮喘受试者的粒细胞上PSGL-1表达的增加导致流动条件下白细胞募集增强。

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摘要

Allergic asthma is increasing in incidence and severity in many industrial countries. Leukocyte recruitment into the airways of affected individuals contributes to the severity of the disease. In this study, whole blood from normal, allergic, asthmatic, or allergic-asthmatic subjects was perfused over immobilized adhesion molecules using an in vitro flow chamber system to determine if there were differences in leukocyte recruitment in these patient populations. Leukocytes from allergic-asthmatic subjects showed a threefold increase in recruitment on P-selectin as compared with normal controls. In both patient populations, the accumulated cells were exclusively neutrophils and eosinophils. Increased granulocyte recruitment was specific for P-selectin, as neither purified E-selectin nor vascular cell adhesion molecule-1 (VCAM-1) supported enhanced leukocyte recruitment from allergic-asthmatics. Leukocyte accumulation on P-selectin was completely blocked by an anti-P-selectin or anti-P-selectin glycoprotein ligand-1 (PSGL-1) monoclonal antibody. Flow cytometry revealed that neutrophils and eosinophils from allergic-asthmatic subjects had increased expression of PSGL-1, whereas expression of another adhesion molecule, L-selectin, was unchanged. PSGL-1 expression on peripheral blood mononuclear cells of allergic-asthmatic patients was unaffected. The increased PSGL-1 expression on granulocytes from allergic-asthmatic patients also led to enhanced leukocyte recruitment on interleukin-4-stimulated human umbilical vein endothelial cells, which express P-selectin and VCAM-1. Thus, increased PSGL-1 expression on granulocytes from allergic-asthmatic subjects resulted in increased leukocyte recruitment on P-selectin under flow conditions.
机译:在许多工业化国家,过敏性哮喘的发病率和严重性正在增加。白细胞募集到受影响个体的气道中导致疾病的严重性。在这项研究中,使用体外流通室系统,通过固定的黏附分子对正常,过敏,哮喘或过敏性哮喘患者的全血进行灌注,以确定这些患者人群中白细胞募集是否存在差异。与正常对照组相比,来自过敏性哮喘受试者的白细胞在P-选择素上的募集增加了三倍。在这两个患者群体中,累积的细胞仅是嗜中性粒细胞和嗜酸性粒细胞。粒细胞募集增加对P-选择素具有特异性,因为纯化的E-选择素和血管细胞粘附分子1(VCAM-1)均不支持过敏性哮喘患者增强的白细胞募集。抗-选择素或抗-选择素糖蛋白配体-1(PSGL-1)单克隆抗体完全阻断了P-选择素上的白细胞积累。流式细胞仪显示,来自过敏性哮喘患者的嗜中性粒细胞和嗜酸性粒细胞具有增加的PSGL-1表达,而另一个粘附分子L-选择素的表达则保持不变。过敏性哮喘患者外周血单个核细胞中PSGL-1的表达不受影响。来自过敏性哮喘患者的粒细胞上PSGL-1表达的增加还导致白细胞介素4刺激的人脐静脉内皮细胞上白细胞募集的增加,白细胞表达P-选择素和VCAM-1。因此,在过敏性哮喘患者的粒细胞上增加的PSGL-1表达导致在流动条件下P-选择蛋白上的白细胞募集增加。

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