Dipeptidase-1 Is an Adhesion Receptor for Neutrophil Recruitment in Lungs and Liver.

Article Details

Citation
Copy to clipboard

Choudhury SR, Babes L, Rahn JJ, Ahn BY, Goring KR, King JC, Lau A, Petri B, Hao X, Chojnacki AK, Thanabalasuriar A, McAvoy EF, Tabaries S, Schraeder C, Patel KD, Siegel PM, Kopciuk KA, Schriemer DC, Muruve DA, Kelly MM, Yipp BG, Kubes P, Robbins SM, Senger DL

Dipeptidase-1 Is an Adhesion Receptor for Neutrophil Recruitment in Lungs and Liver.

Cell. 2019 Aug 22;178(5):1205-1221.e17. doi: 10.1016/j.cell.2019.07.017.

PubMed ID
31442408 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drugs