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IN VITRO CAPILLARY ENDOTHELIAL TUBES AS A MODEL SYSTEM TO STUDY CYTOTOXICITY OF DIESEL PARTICLES
Author(s) -
Chao Ming Wei,
Koslosky John,
Po Iris P,
Gerecke Donald R,
Svoboda Kathy KH,
Laumbach Robert,
Gordon Marion K
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.639.1
Subject(s) - adherens junction , umbilical vein , endothelial stem cell , chemistry , microbiology and biotechnology , paracellular transport , heme oxygenase , biophysics , in vitro , biochemistry , biology , cell , heme , permeability (electromagnetism) , enzyme , cadherin , membrane
Epidemiological studies report acute exposure to diesel exhaust particles (DEP) correlates with an increase in myocardial infarctions within 48 hr. Inhaled DEP gain access to the bloodstream, but how is unknown. We have used human umbilical vein endothelial cells (HUVECs) assembled into in vitro capillary tubes to study the action of DEP. Increasing concentrations of DEP (1‐100 µg/ml) at sizes aound 2.5 um (PM2.5) increase tube cell death, as determined by LDH and TUNEL assays. DEP can be found on tubes and in the lumen of tubes in culture. Endothelial cell‐cell adherens junctional components redistribute away from the plasma membrane after a 24 hr DEP exposure, as assessed by confocal microscopy with vascular endothelial cadherin antibody. Westerns of culture medium demonstrated increased secretion of VEGF‐A with increasing doses of DEP, favoring vascular permeability. Endothelial capillary tubes produce nitrite oxide (NO) and reactive oxygen species (ROS) in response to DEP, and heme oxygenase 1 (HO‐1) and thioredoxin reductase are upregulated . Furthermore, inflammatory markers IL‐1 beta; and IL‐6 are increased in a dose dependent manner as assessed by ELISA. In summary, our in vitro capillary endothelial tube data suggest that DEP make capillaries leaky by disrupting endothelial adherens junctions and inducing secretion of VEGF‐A. The production of potentially damaging ROS is also induced by DEP. Grant Funding Source NIEHS P30ES005022.