Monocyte-endothelial cell interactions in the regulation of vascular sprouting and liver regeneration in mouse
Name
nihms715379.pdf
Size
4.47 MB
Format
Adobe PDF
Checksum (MD5)
662b4aac7eca298be5d4bcbade569b7a
Author(s)
Melgar Lesmes, Pedro
Edelman, Elazer R
Date Issued
May 2015
Journal
Journal of Hepatology
Publisher
Elsevier
Citation
Melgar-Lesmes, Pedro, and Edelman, Elazer R. “Monocyte-Endothelial Cell Interactions in the Regulation of Vascular Sprouting and Liver Regeneration in Mouse.” Journal of Hepatology 63, 4 (October 2015): 917–925 © 2015 European Association for the Study of the Liver
Version
Author's final manuscript
Abstract
Background & Aims Regeneration of the hepatic mass is crucial to liver repair. Proliferation of hepatic parenchyma is intimately dependent on angiogenesis and resident macrophage-derived cytokines. However the role of circulating monocyte interactions in vascular and hepatic regeneration is not well-defined. We investigated the role of these interactions in regeneration in the presence and absence of intact monocyte adhesion. Methods Partial hepatectomy was performed in wild-type mice and those lacking the monocyte adhesion molecule CD11b. Vascular architecture, angiogenesis and macrophage location were analyzed in the whole livers using simultaneous angiography and macrophage staining with fluorescent multiphoton microscopy. Monocyte adhesion molecule expression and sprouting-related pathways were evaluated. Results Resident macrophages (Kupffer cells) did not migrate to interact with vessels whereas infiltrating monocytes were found adjacent to sprouting points. Infiltrated monocytes colocalized with Wnt5a, angiopoietin 1 and Notch-1 in contact points and commensurate with phosphorylation and disruption of VE-cadherin. Mice deficient in CD11b showed a severe reduction in angiogenesis, liver mass regeneration and survival following partial hepatectomy, and developed unstable and leaky vessels that eventually produced an aberrant hepatic vascular network and Kupffer cell distribution. Conclusions Direct vascular interactions of infiltrating monocytes are required for an ordered vascular growth and liver regeneration. These outcomes provide insight into hepatic repair and new strategies for hepatic regeneration.
MIT Department
Institute for Medical Engineering and Science
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.JHEP.2015.05.011
