RRC ID |
34565
|
Author |
Ashina K, Tsubosaka Y, Nakamura T, Omori K, Kobayashi K, Hori M, Ozaki H, Murata T.
|
Title |
Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo.
|
Journal |
PLoS One
|
Abstract |
Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how histamine induces vascular hyperpermeability focusing on the key regulators of vascular permeability, blood flow and endothelial barrier. Degranulation of mast cells by antigen-stimulation or histamine treatment induced vascular hyperpermeability and tissue swelling in mouse ears. These were abolished by histamine H1 receptor antagonism. Intravital imaging showed that histamine dilated vasculature, increased blood flow, while it induced hyperpermeability in venula. Whole-mount staining showed that histamine disrupted endothelial barrier formation of venula indicated by changes in vascular endothelial cadherin (VE-cadherin) localization at endothelial cell junction. Inhibition of nitric oxide synthesis (NOS) by L-NAME or vasoconstriction by phenylephrine strongly inhibited the histamine-induced blood flow increase and hyperpermeability without changing the VE-cadherin localization. In vitro, measurements of trans-endothelial electrical resistance of human dermal microvascular endothelial cells (HDMECs) showed that histamine disrupted endothelial barrier. Inhibition of protein kinase C (PKC) or Rho-associated protein kinase (ROCK), NOS attenuated the histamine-induced barrier disruption. These observations suggested that histamine increases vascular permeability mainly by nitric oxide (NO)-dependent vascular dilation and subsequent blood flow increase and maybe partially by PKC/ROCK/NO-dependent endothelial barrier disruption.
|
Volume |
10(7)
|
Pages |
e0132367
|
Published |
2015-1-1
|
DOI |
10.1371/journal.pone.0132367
|
PII |
PONE-D-15-13075
|
PMID |
26158531
|
PMC |
PMC4497677
|
MeSH |
Animals
Blood Flow Velocity / drug effects
Blood Vessels / drug effects
Blood Vessels / metabolism
Blood Vessels / physiology
Capillary Permeability / drug effects*
Cells, Cultured
Ear, External / blood supply
Ear, External / drug effects
Ear, External / pathology
Endothelial Cells / drug effects*
Endothelial Cells / metabolism
Endothelium, Vascular / drug effects*
Endothelium, Vascular / metabolism
Enzyme Inhibitors / pharmacology
Female
Histamine / metabolism
Histamine / pharmacology*
Histamine Agonists / pharmacology
Humans
Male
Mice
Microscopy, Fluorescence
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide Synthase / antagonists & inhibitors
Nitric Oxide Synthase / metabolism
Phenylephrine / pharmacology
Protein Kinase C / metabolism
Pyridines / pharmacology
Receptors, Histamine H1 / metabolism
Vasoconstrictor Agents / pharmacology
Vasodilation / drug effects
rho-Associated Kinases / metabolism
|
IF |
2.74
|
Times Cited |
47
|
WOS Category
|
MULTIDISCIPLINARY SCIENCES
|
Resource |
Mice |
RBRC00267 |