Pharmacological stabilization of mast cells abrogates late thrombotic events induced by diesel exhaust particles in hamsters.
BACKGROUND
Particulate air pollution is associated with cardiovascular diseases and myocardial infarction (MI).


RESULTS
We investigated the relationship between airway inflammation and thrombosis 24 hours after intratracheal (IT) instillation of diesel exhaust particles (DEP; 50 microg/hamster). Mild thrombosis was induced in the femoral vein by endothelial injury, and the consequences of airway inflammation on thrombogenicity were studied via online video microscopy. Lung inflammation and histamine analysis in bronchoalveolar lavage (BAL) and plasma were performed after pretreatment with dexamethasone (DEX) or sodium cromoglycate (SC). DEP induced airway inflammation and histamine release in BAL and in plasma, and increased thrombosis, without elevating plasma von Willebrand factor (vWF) levels. The IT instillation of 400-nm positively charged polystyrene particles (500 microg/hamster), serving as particles that do not penetrate into the circulation, equally produced airway inflammation, histamine release, and enhanced thrombosis. Histamine in plasma resulted from basophil activation. Intraperitoneal (IP) pretreatment with DEX (5 mg/kg) abolished the DEP-induced histamine increase in BAL and plasma and abrogated airway inflammation and thrombogenicity. The IT pretreatment with DEX (0.5 mg/kg) showed a partial but parallel inhibition of all of these parameters. Pretreatment with SC (40 mg/kg, IP) strongly inhibited airway inflammation, thrombogenicity, and histamine release.


CONCLUSIONS
Our results are compatible with the triggering of mast cell degranulation and histamine release by DEP. Histamine plays an initial central role in airway inflammation, further release of histamine by circulating basophils, and peripheral thrombotic events. Antiinflammatory pretreatment can abrogate the peripheral thrombogenicity by preventing histamine release from mast cells.
Nemmar
Abderrahim
A
Laboratory of Pneumology, Lung Toxicology Unit, Katholieke Universiteit Leuven, Leuven, Belgium.
Hoet
Peter H M
PH
Vermylen
Jos
J
Nemery
Benoit
B
Hoylaerts
Marc F
MF
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006224:Cricetinae; D004205:Cromolyn Sodium / Q000494:pharmacology / Q000627:therapeutic use*; D003594:Cytoplasmic Granules / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000032:analysis; D006636:Histamine Release / Q000187:drug effects; D007322:Instillation, Drug; D008168:Lung / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008647:Mesocricetus; D018715:Microscopy, Video; D009928:Organ Specificity; D010316:Particle Size; D010974:Platelet Aggregation / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000517:prevention & control*; D011137:Polystyrenes / Q000633:toxicity; D013927:Thrombosis / Q000139:chemically induced / Q000517:prevention & control*; D014132:Trachea; D014657:Vasculitis / Q000139:chemically induced / Q000517:prevention & control*; D001335:Vehicle Emissions / Q000633:toxicity*; D014841:von Willebrand Factor / Q000032:analysis
D000393:Air Pollutants; D000893:Anti-Inflammatory Agents; D011137:Polystyrenes; D001335:Vehicle Emissions; D014841:von Willebrand Factor; D003907:Dexamethasone; D006632:Histamine; D004205:Cromolyn Sodium