Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo

• DOI: 10.1371/journal.pone.0132367
• Publication Date: 2015-07-09T13:52:10Z
• Authors: Kohei Ashina; Yoshiki Tsubosaka; Tatsuro Nakamura; Keisuke Omori; Koji Kobayashi; Masatoshi Hori; Hiroshi Ozaki; Takahisa Murata
• Keywords: Vascular permeability

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 induces hyperpermeability focusing on the key regulators blood flow and endothelial barrier. Degranulation cells by antigen-stimulation or treatment induced tissue swelling mouse ears. These were abolished H1 receptor antagonism. Intravital imaging showed that dilated vasculature, increased flow, while it venula. Whole-mount staining disrupted barrier formation venula indicated changes cadherin (VE-cadherin) localization at cell junction. Inhibition nitric oxide synthesis (NOS) L-NAME vasoconstriction phenylephrine inhibited histamine-induced increase without changing VE-cadherin localization. In vitro, measurements trans-endothelial electrical resistance human dermal microvascular (HDMECs) protein kinase C (PKC) Rho-associated (ROCK), NOS attenuated disruption. observations suggested permeability (NO)-dependent dilation subsequent maybe partially PKC/ROCK/NO-dependent