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Eosinophil Tissue Recruitment to Sites of Allergic Inflammation in the Lung Is Platelet Endothelial Cell Adhesion Molecule Independent

机译:嗜酸性粒细胞组织招募到肺部过敏性炎症是血小板内皮细胞粘附分子独立的。

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Platelet endothelial cell adhesion molecule (PECAM or CD31) is a cell adhesion molecule expressed on circulating leukocytes and endothelial cells that plays an important role in mediating neutrophil and monocyte transendothelial migration in vivo. In this study, we investigated whether eosinophils, like neutrophils and monocytes, utilize PECAM for tissue recruitment to sites of allergic inflammation in vivo. Eosinophils express similar levels of PECAM as neutrophils as assessed by FACS analysis. RT-PCR studies demonstrate that eosinophils like neutrophils express the six extracellular domains of PECAM. Eosinophils exhibit homophilic binding to recombinant PECAM as assessed in a single-cell micropipette adhesion assay able to measure the biophysical strength of adhesion of eosinophils to recombinant PECAM. The strength of eosinophil adhesion to recombinant PECAM is the same as that of neutrophil binding to recombinant PECAM and can be inhibited with an anti-PECAM Ab. Although eosinophils express functional PECAM, anti-PECAM Abs did not inhibit bronchoalveolar lavage eosinophilia, lung eosinophilia, and airway hyperreactivity to methacholine in a mouse model of OVA-induced asthma in vivo. Thus, in contrast to studies that have demonstrated that neutrophil and monocyte tissue recruitment is PECAM dependent, these studies demonstrate that eosinophil tissue recruitment in vivo in this model is PECAM independent.
机译:血小板内皮细胞粘附分子(PECAM或CD31)是在循环白细胞和内皮细胞上表达的细胞粘附分子,在体内介导嗜中性粒细胞和单核细胞跨内皮迁移中起重要作用。在这项研究中,我们调查了嗜酸性粒细胞是否像嗜中性粒细胞和单核细胞一样,利用PECAM将组织募集到体内变应性炎症的部位。通过FACS分析评估,嗜酸性粒细胞表达的PECAM水平与嗜中性粒细胞相似。 RT-PCR研究表明嗜酸性粒细胞如嗜中性粒细胞表达PECAM的六个胞外域。如在单细胞微量移液管粘附测定中所评估的,嗜酸性粒细胞表现出对重组PECAM的同源结合,能够测定嗜酸性粒细胞对重组PECAM的粘附的生物物理强度。嗜酸性粒细胞对重组PECAM的粘附强度与嗜中性粒细胞与重组PECAM的结合强度相同,并且可以被抗PECAM Ab抑制。尽管嗜酸性粒细胞表达功能性PECAM,但在小鼠OVA诱发的哮喘小鼠模型中,抗PECAM Abs不能抑制支气管肺泡灌洗嗜酸性粒细胞增多,肺嗜酸性粒细胞增多和气道对乙酰甲胆碱的高反应性。因此,与已经证明嗜中性粒细胞和单核细胞组织募集是PECAM依赖性的研究相反,这些研究表明在该模型中体内嗜酸性粒细胞组织募集是PECAM非依赖性的。

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