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Diesel-Enriched Particulate Matter Functionally Activates Human Dendritic Cells

¹ Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; ² The Johns Hopkins Bloomberg School of Hygiene and Public Health, Baltimore, Maryland; ³ Division of Pulmonary and Critical Care Medicine, and ⁴ Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York

Correspondence and requests for reprints should be addressed to Dr. Marc Adrian Williams, Division of Pulmonary and Critical Care Medicine, University of Rochester School of Medicine and Dentistry, KMRB Room 2-9609, 601 Elmwood Avenue, Box 692, Rochester, NY 14642-8692. E-mail: marc_williams{at}urmc.rochester.edu

Epidemiologic studies have associated exposure to airborne particulate matter (PM) with exacerbations of asthma. It is unknown how different sources of PM affect innate immunity. We sought to determine how car- and diesel exhaust–derived PM affects dendritic cell (DC) activation. DC development was modeled using CD34+ hematopoietic progenitors. Airborne PM was collected from exhaust plenums of Fort McHenry Tunnel providing car-enriched particles (CEP) and diesel-enriched particles (DEP). DC were stimulated for 48 hours with CEP, DEP, CD40-ligand, or lipopolysaccharide. DC activation was assessed by flow cytometry, enzyme-linked immunosorbent assay, and standard culture techniques. DEP increased uptake of fluorescein isothiocyanate–dextran (a model antigen) by DC. Diesel particles enhanced cell-surface expression of co-stimulatory molecules (e.g., CD40 [P < 0.01] and MHC class II [P < 0.01]). By contrast, CEP poorly affected antigen uptake and expression of cell surface molecules, and did not greatly affect cytokine secretion by DC. However, DEP increased production of TNF, IL-6, and IFN- (P < 0.01), IL-12 (P < 0.05), and vascular endothelial growth factor (P < 0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g., enhanced IL-13 and IL-18 and suppressed IFN- production). CD4+ T cells were not functionally activated on exposure to either DEP or CEP. Car- and diesel-enriched particles exert a differential effect on DC activation. Our data support the hypothesis that DEP (and to a lesser extent CEP) regulate important functional aspects of human DC, supporting an adjuvant role for this material.

Key Words: asthma • allergy • innate immunity • Toll-like receptors • pollution

CLINICAL RELEVANCE This study describes the immunological effects of diesel and car-enriched particulates on dendritic cell activation and their promotion of a Th2-like cytokine response by CD4+ T cells. This is a novel observation relevant to our understanding of the immune adjuvant effects of environmental pollutants and pathogenesis of allergic pulmonary diseases.