医学
单核细胞
炎症
缺血
再灌注损伤
肾缺血
急性肾损伤
管周毛细血管
药理学
肾
免疫学
内科学
作者
Arthur Lau,Jennifer J. Rahn,Mona Chappellaz,Hyunsoo Chung,Hallgrímur Benediktsson,Dominique Bihan,Anne von Mäßenhausen,Andreas Linkermann,Craig N. Jenne,Stephen M. Robbins,Donna L. Senger,Ian A. Lewis,Justin Chun,Daniel A. Muruve
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2022-02-04
卷期号:8 (5)
被引量:25
标识
DOI:10.1126/sciadv.abm0142
摘要
The mechanisms that drive leukocyte recruitment to the kidney are incompletely understood. Dipeptidase-1 (DPEP1) is a major neutrophil adhesion receptor highly expressed on proximal tubular cells and peritubular capillaries of the kidney. Renal ischemia reperfusion injury (IRI) induces robust neutrophil and monocyte recruitment and causes acute kidney injury (AKI). Renal inflammation and the AKI phenotype were attenuated in Dpep1-/- mice or mice pretreated with DPEP1 antagonists, including the LSALT peptide, a nonenzymatic DPEP1 inhibitor. DPEP1 deficiency or inhibition primarily blocked neutrophil adhesion to peritubular capillaries and reduced inflammatory monocyte recruitment to the kidney after IRI. CD44 but not ICAM-1 blockade also decreased neutrophil recruitment to the kidney during IRI and was additive to DPEP1 effects. DPEP1, CD44, and ICAM-1 all contributed to the recruitment of monocyte/macrophages to the kidney following IRI. These results identify DPEP1 as a major leukocyte adhesion receptor in the kidney and potential therapeutic target for AKI.
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