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Mark W. Frampton,^1,2 Judith C. Stewart,¹ Günter Oberdörster,² Paul E. Morrow,² David Chalupa,¹ Anthony P. Pietropaoli,¹ Lauren M. Frasier,¹ Donna M. Speers,¹ Christopher Cox,³ Li-Shan Huang,⁴ and Mark J. Utell^1,2

¹Department of Medicine, and ²Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York, USA; ³Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA; ⁴Department of Biostatistics, University of Rochester School of Medicine, Rochester, New York, USA

Abstract
Ultrafine particles (UFPs ; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter ~ 25 nm, geometric standard deviation ~ 1.6) , for 2 hr, in three separate protocols: 10 µg/m³ at rest, 10 and 25 µg/m³ with exercise, and 50 µg/m³ with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 µg/m³ UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 µg/m³ UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4⁺ T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed. Key words: blood leukocytes, human, monocytes, ultrafine particles. Environ Health Perspect 114: 51-58 (2006) . doi:10.1289/ehp.7962 available via http://dx.doi.org/ [Online 20 September 2005]

Address correspondence to M.W. Frampton, University of Rochester Medical Center, 601 Elmwood Ave., Box 692, Rochester, NY 14642-8692 USA. Telephone: (585) 275-4861. Fax: (585) 273-1114. E-mail: mark_frampton@urmc.rochester.edu

This work was supported by contract 98-19 from the Health Effects Institute (HEI) ; U.S. Environmental Protection Agency (EPA) assistance agreements R826781-01 and R827354-01 ; grants RO1 ES011853, RR00044, and ES01247 from the National Institutes of Health ; and grant 4913-ERTER-ES-99 from the New York State Energy Research and Development Authority.

Some of the research described in this article was conducted under contract to the HEI, an organization jointly funded by the U.S. EPA (assistance agreement X-812059) and automotive manufacturers. The contents of this article do not necessarily reflect the views of the HEI, nor do they necessarily reflect the policies of the U.S. EPA or of automotive manufacturers.

The authors declare they have no competing financial interests.

Received 25 January 2005 ; accepted 20 September 2005.