Perivascular Macrophages Limit Permeability

Huanhuan He, Julia J. Mack, Esra Güç, Carmen M. Warren, Mario Leonardo Squadrito, Witold W. Kilarski, Caroline Baer, Ryan D. Freshman, Austin I. McDonald, Safiyyah Ziyad, Melody A. Swartz, Michele De Palma, M. Luisa Iruela-Arispe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Objective - Perivascular cells, including pericytes, macrophages, smooth muscle cells, and other specialized cell types, like podocytes, participate in various aspects of vascular function. However, aside from the well-established roles of smooth muscle cells and pericytes, the contributions of other vascular-associated cells are poorly understood. Our goal was to ascertain the function of perivascular macrophages in adult tissues under nonpathological conditions. Approach and Results - We combined confocal microscopy, in vivo cell depletion, and in vitro assays to investigate the contribution of perivascular macrophages to vascular function. We found that resident perivascular macrophages are associated with capillaries at a frequency similar to that of pericytes. Macrophage depletion using either clodronate liposomes or antibodies unexpectedly resulted in hyperpermeability. This effect could be rescued when M2-like macrophages, but not M1-like macrophages or dendritic cells, were reconstituted in vivo, suggesting subtype-specific roles for macrophages in the regulation of vascular permeability. Furthermore, we found that permeability-promoting agents elicit motility and eventual dissociation of macrophages from the vasculature. Finally, in vitro assays showed that M2-like macrophages attenuate the phosphorylation of VE-cadherin upon exposure to permeability-promoting agents. Conclusions - This study points to a direct contribution of macrophages to vessel barrier integrity and provides evidence that heterotypic cell interactions with the endothelium, in addition to those of pericytes, control vascular permeability.

Original languageEnglish (US)
Pages (from-to)2203-2212
Number of pages10
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number11
StatePublished - Nov 1 2016


  • capillaries
  • capillary permeability
  • cell communication
  • endothelial cells
  • macrophages

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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