Diesel-enriched particulate matter functionally activates human dendritic cells
Diesel-enriched particulate matter functionally activates human dendritic cells
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DOI：
10.1165/rcmb.2007-0199oc
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发表时间：
2007-12-01
影响因子：
6.4
通讯作者：
Williams, Marc A.
中科院分区：
文献类型：
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作者：
Porter, Michael;Karp, Matthew;Williams, Marc A.
流行病学研究已将暴露于空气中的颗粒物（PM）与哮喘加重联系起来。目前尚不清楚不同来源的PM如何影响先天免疫。我们试图确定汽车和柴油尾气产生的PM如何影响树突状细胞（DC）的激活。使用CD34+造血祖细胞模拟DC发育。从麦克亨利堡隧道的排气室内收集空气中的PM，其中包括汽车富集颗粒（CEP）和柴油富集颗粒（DEP）。用CEP、DEP、cd40配体或脂多糖刺激DC 48小时。通过流式细胞术、酶联免疫吸附试验和标准培养技术评估DC激活。DEP增加DC对异硫氰酸-葡聚糖荧光素（一种模型抗原）的摄取。柴油颗粒增强了细胞表面共刺激分子（如CD40 [P < 0.01]和MHC II类[P < 0.01]）的表达。相比之下，CEP对抗原摄取和细胞表面分子表达的影响较小，对DC分泌的细胞因子影响不大。然而，DEP增加了TNF、IL-6和ifn - γ (P< 0.01)、IL-12 （P< 0.05）和血管内皮生长因子（P< 0.001）的产生。在pm暴露的DC和同种异体CD4+ T细胞的共刺激试验中，CEP和DEP都指导th2样细胞因子产生模式（例如，增强IL-13和IL-18并抑制ifn - γ产生）。CD4+ T细胞在暴露于DEP或CEP时都没有功能激活。汽车和柴油富集颗粒对直流活化的影响不同。我们的数据支持DEP（以及较小程度的CEP）调节人类DC的重要功能方面的假设，支持该材料的辅助作用。
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.