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

Abstract

Highlights d Dipeptidase 1 (DPEP1) serves as a vascular adhesion molecule in lungs and liver d DPEP1 acts as a physical adhesion receptor independent of its dipeptidase activity d Targeting DPEP1 reduces mortality in murine models of sepsis

Neutrophils in liver diseases: pathogenesis and therapeutic targets

“…5 Dipeptidase-1, a major adhesion receptor on hepatic endothelial cells, also mediates neutrophil adhesion in an enzyme activityindependent manner. 6 Apoptotic neutrophils are eliminated mainly by macrophages, which contributes to localized tissue inflammation. Meanwhile, activated macrophages secrete both G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) to slow neutrophil apoptosis.…”

The Secretive Life of Neutrophils Revealed by Intravital Microscopy

“…This work indicates that the lung is an important host defense niche for the detection and capture of systemic pathogens, and requires cooperation between the vascular endothelium and marginated neutrophils (Yipp et al, 2017). In the search for new adhesion molecules that support neutrophil retention in the lung during inflammation, an in vivo functional screen surprisingly identified dipeptidase-1 (DEPEP1) (Rajotte and Ruoslahti, 1999;Choudhury et al, 2019). DEPEP1, a membrane enzyme expressed by activated pulmonary endothelium, was shown to support neutrophil adhesion, independent of its enzymatic activity.…”

“…DEPEP1, a membrane enzyme expressed by activated pulmonary endothelium, was shown to support neutrophil adhesion, independent of its enzymatic activity. Moreover, genetic deletion studies and use of a blocking peptide showed that neutrophil adhesion and recruitment in the inflamed lung was significantly attenuated in the absence of DEPEP1 during sepsis (Choudhury et al, 2019). Finally, when the DEPEP1 blocking peptide was used therapeutically in mice administered with a lethal dose of LPS, it showed a remarkable survival effect and an impressive reduction in neutrophil recruitment into the inflamed lung (Choudhury et al, 2019).…”

“…Moreover, genetic deletion studies and use of a blocking peptide showed that neutrophil adhesion and recruitment in the inflamed lung was significantly attenuated in the absence of DEPEP1 during sepsis (Choudhury et al, 2019). Finally, when the DEPEP1 blocking peptide was used therapeutically in mice administered with a lethal dose of LPS, it showed a remarkable survival effect and an impressive reduction in neutrophil recruitment into the inflamed lung (Choudhury et al, 2019). With respect to the focus of this review, highlighting how IVM has been key to advancing our understanding and identifying the molecular pathways regulating neutrophil trafficking, this research is notable in that the initial screen involved using confocal IVM to identify a peptide that localized to both the lung and liver endothelium after LPS treatment and reduced neutrophil accumulation in these tissues.…”

Disruption of a C69-Family Cysteine Dipeptidase Gene Enhances Heat Shock and UV-B Tolerances in Metarhizium acridum

“…At present, the research of dipeptidase mainly focuses on animal (O'Dwyer et al, 2009;Andreyeva et al, 2019;Choudhury et al, 2019), human pathogenic bacteria (Chang et al, 2010;Toyotome et al, 2015) or plant pathogenic bacteria (Kumar et al, 2014). Function reports of dipeptidases are mostly limited to virulence and growth in microorganisms, while there is little information regarding the effect of dipeptidases on stress tolerance in microorganisms.…”