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Endothelial repair is dependent on CD11c + leukocytes to establish regrowing endothelial sheets with high cellular density
Author(s) -
Yrlid Ulf,
Holm Maricris,
Levin Malin,
Alsén Samuel,
Lindbom Malin,
Glise Lars,
Bergh Niklas,
Borén Jan,
Fogelstrand Per
Publication year - 2019
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.4a1017-402rr
Subject(s) - biology , cd11c , microbiology and biotechnology , endothelial stem cell , immunology , genetics , phenotype , gene , in vitro
Abstract Endothelial injury makes the vessel wall vulnerable to cardiovascular diseases. Injured endothelium regenerates by collective sheet migration, that is, the endothelial cells coordinate their motion and regrow as a sheet of cells with retained cell‐cell contacts into the wounded area. Leukocytes appear to be involved in endothelial repair in vivo ; however, little is known about their identity and role in the reparative sheet migration process. To address these questions, we developed a high‐quality en face technique that enables visualizing of leukocytes and endothelial cells simultaneously following an endoluminal scratch wound injury of the mouse carotid artery. We discovered that regrowing endothelium forms a broad proliferative front accompanied by CD11c + leukocytes. Functionally, the leukocytes were dispensable for the initial migratory response of the regrowing endothelial sheet, but critical for the subsequent formation and maintenance of a front zone with high cellular density. Marker expression analyses, genetic fate mapping, phagocyte targeting experiments, and mouse knock‐out experiments indicate that the CD11c + leukocytes were mononuclear phagocytes with an origin from both Ly6C high and Ly6C low monocytes. In conclusion, CD11c + mononuclear phagocytes are essential for a proper endothelial regrowth following arterial endoluminal scratch injury. Promoting the endothelial‐preserving function of CD11c + leukocytes may be a strategy to enhance endothelial repair following surgical and endovascular procedures.