Published in the AAAS journal Science Advances this paper by key members of the Arch Biopartners scientific team led by Dr. Daniel Muruve at the University of Calgary, and their collaborators, demonstrated the mechanism by which DPEP-1 regulates the recruitment of leukocytes (i.e. inflammation) to the kidney following ischemia reperfusion injury, which is injury that occurs after a reduction in blood flow to the kidney. Ischemia reperfusion injury is a common cause of AKI in humans undergoing cardiac surgery or kidney transplantation.

Importantly, the study also confirmed the mechanism of action of two DPEP-1 inhibitors, the LSALT peptide (Metablok) and cilastatin that effectively protected the kidney during ischemia reperfusion injury. Both the LSALT peptide and cilastatin are protected by composition and method of use patents for AKI respectively and held by Arch Biopartners.

Publication Details

Science Advances, ...

Authors

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

Details

Published in the journal Cell, Volume 178, Issue 5, Pg1205-1221.E17, August 22, 2019
DOI: https://doi.org/10.1016/j.cell.2019.07.017
Read the full publication online at Cell or view the PDF version

Highlights

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

Abstract

A hallmark feature of inflammation is the orchestrated recruitment ...

Authors

Arthur Lau, Hyunjae Chung, Takanori Komada, Jaye M. Platnich, Christina F. Sandall, Saurav Roy Choudhury, Justin Chun, Victor Naumenko, Bas G.J. Surewaard, Michelle C. Nelson, Annegret Ulke-Lemée, Paul L. Beck, Hallgrimur Benediktsson, Anthony M. Jevnikar, Sarah L. Snelgrove, Michael J. Hickey, Donna L. Senger, Matthew T. James, Justin A. Macdonald, Paul Kubes, Craig N. Jenne, Daniel A. Muruve

Details

Published in JCI, The Journal of Clinical Investigation, June 4, 2018
J Clin Invest. 2018 Jul 2;128(7):2894-2913. doi: 10.1172/JCI96640. Epub 2018 Jun 4.
Read the article online at JCI read the PDF version (JCI) – also available from the NIH PMC

Abstract

Radiographic contrast agents cause acute kidney injury (AKI), yet the underlying pathogenesis is poorly understood. Nod-like receptor pyrin containing 3–deficient (Nlrp3-deficient) mice displayed reduced epithelial cell injury and inflammation in the kidney in a model of contrast-induced AKI ...