Data from: Acute cytotoxicity and increased vascular endothelial growth factor after in vitro nitrogen mustard vapor exposure

RATIONALE:  Nitrogen mustard (NM) is a highly toxic alkylating
agent.  It is classified as chemical threat due to its potential
use as a warfare agent.  When inhaled, mustard exposure can cause
both acute and chronic lung injury.  The aims of this study are
to develop an in vitro culture system for modeling mustard-induced airway
injury and to identify growth factors contributing to airway pathology.
METHODS:  Primary human bronchial epithelial cells co-cultured
with primary human pulmonary endothelial cells were exposed to NM (25, 50,
100, 250 or 500 µM) or PBS (control) for 1 hour.  Lactate
dehydrogenase (LDH) and trans-epithelial electrical resistance (TEER) were
measured prior to and 24 hours after NM exposure.  Endothelial
cultures were then stained for live/dead staining.  Exposed
airway media was also analyzed for growth factors using Luminex multiplex
technology.  RESULTS:  A one-hour NM vapor exposure
increased supernatant LDH and decreased TEER at 24 hours for all cultures
exposed to NM concentrations greater than or equal to 50 µM. 
Evidence of endothelial cell death occurred at NM concentrations of 250
and 500 µM. Vascular endothelial growth factor (VEGF) signaling,
specifically VEGF-A and placental growth factor (PlGF), increased in
NM-exposed co-culture media compared to PBS
controls.    CONCLUSIONS:  NM vapor
exposure causes significant airway epithelial and endothelial
injury.  Increased VEGF signaling occurred in airway co-cultures
exposed to higher NM concentrations with concurrent endothelial cell
death.  Future studies are required to validate the role of VEGF
signaling in both acute and chronic mustard-induced airway
pathology.