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2016 ; 36
(11
): 2203-2212
Nephropedia Template TP
He H
; Mack JJ
; Güç E
; Warren CM
; Squadrito ML
; Kilarski WW
; Baer C
; Freshman RD
; McDonald AI
; Ziyad S
; Swartz MA
; De Palma M
; Iruela-Arispe ML
Arterioscler Thromb Vasc Biol
2016[Nov]; 36
(11
): 2203-2212
PMID27634833
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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.
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