2019年8月22日出版的《细胞》报道了加拿大卡尔加里大学Donna L. Senger小组的最新成果，他们发现二肽酶-1是肺和肝内中性粒细胞募集的粘附受体。
利用无偏倚的体内功能性筛选方法，研究人员发现了一种肺和肝归巢肽，它可以阻碍中性粒细胞向这些器官的募集。使用生物化学、遗传和共焦活体成像方法，研究人员确定二肽酶-1（DPEP1）作为粘附受体招募中性粒细胞到肝和肺，并且这种招募并不依赖于二肽酶-1的酶活性。重要的是，DPEP1的基因缺失或利用肽段阻断DPEP1的功能可以显著减少了中性粒细胞向肺和肝脏的招募，并改善内毒素血症模型动物的存活率。研究人员的数据证明DPEP1是肺和肝内皮的主要粘附受体，并确定DEPE1可以作为由中性粒细胞引起的肺部炎症性疾病的治疗靶点。
据介绍，炎症标志性的特征是从血液招募中性粒细胞到炎症部位。尽管选择蛋白和整合素介导了许多组织中中性粒细胞的募集，但它们在肺和肝中几乎不发挥作用。
附：英文原文
Title: Dipeptidase-1 Is an Adhesion Receptor for Neutrophil Recruitment in Lungs and Liver
Author: Saurav Roy Choudhury,Liane Babes,Jennifer J. Rahn,Bo-Young Ahn.Kimberly-Ann R. Goring,Jennifer C. King,Arthur Lau,Björn Petri,Xiaoguang Hao,Andrew K. Chojnacki,Ajitha Thanabalasuriar,Erin F. McAvoy,Sébastien Tabariès,Christoph Schraeder,Kamala D. Patel,Peter M. Siegel,Karen A. Kopciuk,David C. Schriemer,Daniel A. Muruve,Margaret M. Kelly,Bryan G. Yipp,Paul Kubes,Stephen M. Robbins,Donna L. Senger
Issue&Volume: Volume 178 Issue 5
Abstract: A hallmark feature of inflammation is the orchestrated recruitment of neutrophils from the bloodstream into inflamed tissue. Although selectins and integrins mediate recruitment in many tissues, they have a minimal role in the lungs and liver. Exploiting an unbiased in vivo functional screen, we identified a lung and liver homing peptide that functionally abrogates neutrophil recruitment to these organs. Using biochemical, genetic, and confocal intravital imaging approaches, we identified dipeptidase-1 (DPEP1) as the target and established its role as a physical adhesion receptor for neutrophil sequestration independent of its enzymatic activity. Importantly, genetic ablation or functional peptide blocking of DPEP1 significantly reduced neutrophil recruitment to the lungs and liver and provided improved survival in models of endotoxemia. Our data establish DPEP1 as a major adhesion receptor on the lung and liver endothelium and identify a therapeutic target for neutrophil-driven inflammatory diseases of the lungs.
DOI: https://doi.org/10.1016/j.cell.2019.07.017
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30782-2