This Article Full Text Full Text (PDF) All Versions of this Article: 110/12/1670    most recent 01.CIR.0000142053.13921.21v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nemmar, A. Articles by Hoylaerts, M. F. Search for Related Content PubMed PubMed Citation Articles by Nemmar, A. Articles by Hoylaerts, M. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CROMOLYN DEXAMETHASONE HISTAMINE Medline Plus Health Information Pneumonia Vasculitis Related Collections Arterial thrombosis Thrombosis risk factors Platelets Animal models of human disease

(Circulation. 2004;110:1670-1677.)
© 2004 American Heart Association, Inc.

Vascular Medicine

Pharmacological Stabilization of Mast Cells Abrogates Late Thrombotic Events Induced by Diesel Exhaust Particles in Hamsters

From the Laboratory of Pneumology, Lung Toxicology Unit (A.N., P.H.M.H., B.N.), and the Center for Molecular and Vascular Biology (J.V., M.F.H.), Katholieke Universiteit Leuven, Leuven, Belgium.

Correspondence to Prof B. Nemery, Katholieke Universiteit Leuven, Laboratory of Pneumology, Lung Toxicology Unit, Herestraat, 49, B-3000 Leuven, Belgium. E-mail ben.nemery{at}med.kuleuven.ac.be

Received October 31, 2003; de novo received February 26, 2004; revision received April 29, 2004; accepted May 3, 2004.

Background— Particulate air pollution is associated with cardiovascular diseases and myocardial infarction (MI).

Methods and Results— We investigated the relationship between airway inflammation and thrombosis 24 hours after intratracheal (IT) instillation of diesel exhaust particles (DEP; 50 µg/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 µg/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.

Key Words: lung • respiration • thrombosis • air pollution

This article has been cited by other articles:

				C. G. Tankersley, H. C. Champion, E. Takimoto, K. Gabrielson, D. Bedja, V. Misra, H. El-Haddad, R. Rabold, and W. Mitzner Exposure to inhaled particulate matter impairs cardiac function in senescent mice Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R252 - R263. [Abstract] [Full Text] [PDF]

				R. D. Brook Air Pollution: What Is Bad for the Arteries Might Be Bad for the Veins Arch Intern Med, May 12, 2008; 168(9): 909 - 911. [Full Text] [PDF]

				A. Nemmar, K. Melghit, and B. H. Ali The Acute Proinflammatory and Prothrombotic Effects of Pulmonary Exposure to Rutile TiO2 Nanorods in Rats Experimental Biology and Medicine, May 1, 2008; 233(5): 610 - 619. [Abstract] [Full Text] [PDF]

				I. N. Krivoshto, J. R. Richards, T. E. Albertson, and R. W. Derlet The Toxicity of Diesel Exhaust: Implications for Primary Care J Am Board Fam Med, January 1, 2008; 21(1): 55 - 62. [Abstract] [Full Text] [PDF]

				N. G. Kounis, G. N. Kounis, S. N. Kouni, G. D. Soufras, C. Niarchos, and A. Mazarakis Allergic Reactions Following Implantation of Drug-Eluting Stents: A Manifestation of Kounis Syndrome? J. Am. Coll. Cardiol., August 1, 2006; 48(3): 592 - 593. [Full Text] [PDF]

				T. Nawrot, A. Nemmar, and B. Nemery Update in environmental and occupational medicine 2005. Am. J. Respir. Crit. Care Med., May 1, 2006; 173(9): 948 - 952. [Full Text] [PDF]

				N. G. Kounis, G. N. Kounis, S. N. Kouni, and G. D. Soufras The heart, the brain, and the Kounis syndrome Eur. Heart J., March 2, 2006; 27(6): 757 - 757. [Full Text] [PDF]

				N. G Kounis, S. N Kouni, and C. M Koutsojannis Myocardial infarction after aspirin treatment, and Kounis syndrome J R Soc Med, June 1, 2005; 98(6): 296 - 296. [Full Text] [PDF]

				A. Nemmar, B. Nemery, P. H. M. Hoet, N. Van Rooijen, and M. F. Hoylaerts Silica Particles Enhance Peripheral Thrombosis: Key Role of Lung Macrophage-Neutrophil Cross-Talk Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 872 - 879. [Abstract] [Full Text] [PDF]