Endothelial repair is dependent on CD11c+ leukocytes to establish regrowing endothelial sheets with high cellular density. Issue 1 (28th September 2018)

• Record Type: Journal Article
• Authors: Yrlid, Ulf; Holm, Maricris; Levin, Malin; Alsén, Samuel; Lindbom, Malin; Glise, Lars; Bergh, Niklas; Borén, Jan; Fogelstrand, Per
• Is Part Of: Journal of leukocyte biology. Volume 105:Issue 1(2019)
• Page Start: 195
• Page End: 202
• Publication Date: 2018-09-28
• Subjects: injury -- repair; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.4A1017-402RR
• Languages: English
• ISSNs: 0741-5400

Abstract

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. CD11c + mononuclear phagocytes are recruited specifically to regenerating endothelium following vascular injury to orchestrate endothelial sheet migration.