title: Diesel-enriched particulate matter functionally activates human dendritic cells.
abstract: 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-gamma (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-gamma 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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Porter
authors.forename: Matthew
authors.initials: M
authors.lastname: Karp
authors.forename: Smruti
authors.initials: S
authors.lastname: Killedar
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Bauer
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: D'Ann
authors.initials: D
authors.lastname: Williams
authors.forename: Patrick
authors.initials: P
authors.lastname: Breysse
authors.forename: Steve N
authors.initials: SN
authors.lastname: Georas
authors.forename: Marc A
authors.initials: MA
authors.lastname: Williams
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D052638:Particulate Matter / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D001335:Vehicle Emissions; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D052638:Particulate Matter; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D001335:Vehicle Emissions; D000097802:CD83 Antigen