Meningeal lymphatic endothelial cells fulfill scavenger endothelial cell function and cooperate with microglia in waste removal from the brain. Issue 1 (6th September 2021)

• Record Type: Journal Article
• Authors: Huisman, Yvonne; Uphoff, Katharina; Berger, Michael; Dobrindt, Ulrich; Schelhaas, Mario; Zobel, Thomas; Bussmann, Jeroen; van Impel, Andreas; Schulte‐Merker, Stefan
• Is Part Of: Glia. Volume 70:Issue 1(2022)
• Page Start: 35
• Page End: 49
• Publication Date: 2021-09-06
• Subjects: brain lymphatic endothelial cells -- macromolecular uptake -- meningeal lymphatic endothelial cells -- microglia -- scavenger endothelial cells -- zebrafish; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.24081
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Brain lymphatic endothelial cells (BLECs) constitute a group of loosely connected endothelial cells that reside within the meningeal layer of the zebrafish brain without forming a vascular tubular system. BLECs have been shown to readily endocytose extracellular cargo molecules from the brain parenchyma, however, their functional relevance in relation to microglia remains enigmatic. We here compare their functional uptake efficiency for several macromolecules and bacterial components with microglia in a qualitative and quantitative manner in 5‐day‐old zebrafish embryos. We find BLECs to be significantly more effective in the uptake of proteins, polysaccharides and virus particles as compared to microglia, while larger particles like bacteria are only ingested by microglia but not by BLECs, implying a clear distribution of tasks between the two cell types in the brain area. In addition, we compare BLECs to the recently discovered scavenger endothelial cells (SECs) of the cardinal vein and find them to accept an identical set of substrate molecules. Our data identifies BLECs as the first brain‐associated SEC population in vertebrates, and demonstrates that BLECs cooperate with microglia to remove particle waste from the brain. Main Points: BLECs serve as a scavenger endothelial cell population in the brain meninges. Microglia and BLECs significantly differ in their uptake efficiency for different substances. Microglia remove bacterial components, BLECs take up proteins and polysaccharides.