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
Mice RBRC00267