Wichmann Gunnar, Franck Ulrich, Herbarth Olf, Rehwagen Martina, Dietz Andreas, Massolo Laura, Ronco Alicia, Müller Andrea
Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Liebigstrasse 26, D-04103 Leipzig, Germany.
Toxicology. 2009 Mar 29;257(3):127-36. doi: 10.1016/j.tox.2008.12.024. Epub 2008 Dec 31.
Immunomodulatory effects of chemicals adsorbed to particles with aerodynamic diameter below 0.49 microm (PM(0.5)) collected in winter 2001 at three sampling points (industrial area [LPIn], traffic-influenced urban area [LPCi], and control area [LPCo]) of La Plata, Argentina, were investigated. The sampling of particulate matter was carried out with high-volume collectors using cascade impactors. PM(0.5)-adsorbed compounds were hexane-extracted by accelerated solvent extraction. For immunological investigations, human peripheral blood lymphocytes were activated by phytohemagglutinin and exposed to dimethyl-sulfoxide dilutions of PM(0.5)-extracts for 24h. Vitality/proliferation was quantified using MTT, released interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by ELISA. Cytokine production but not vitality/proliferation was significantly suppressed by all of the highest extract concentrations. Generally, suppression of IFN-gamma by PM(0.5)-extracts was stronger than those of IL-4. Based on administered mass of PM(0.5), all extracts suppressed IFN-gamma production nearly uniform. Contrary, LPCi-extracts exerted maximum IFN-gamma suppression based either on air volume or regarding PM(0.5)-adsorbed PAH. Also the ranking of PM(0.5)-associated effects on IL-4 production differs in dependence of the chosen reference points, either mass or [microg/ml] or air volume [m(3)/ml] related dust quantities in cell culture. Based on the corresponding air volume, LPCi-extracts inhibited IL-4 production to the maximum extend, whereas suppression of IL-4 was comparable based on concentrations. This indicates that not only the disparate PM(0.5)-masses in air cause varying impacts, but also that disparities in PM(0.5)-adsorbed chemicals provoke different effects on immune responses and shifts in the regulatory balance that might have implications for allergy and cancer development.
2001年冬季，在阿根廷拉普拉塔的三个采样点（工业区[LPIn]、受交通影响的市区[LPCi]和对照区[LPCo]）采集了空气动力学直径小于0.49微米的颗粒物（PM(0.5)），研究了吸附在这些颗粒物上的化学物质的免疫调节作用。使用级联撞击器通过大容量收集器进行颗粒物采样。采用加速溶剂萃取法用己烷萃取吸附在PM(0.5)上的化合物。在免疫学研究中，用植物血凝素激活人外周血淋巴细胞，并将其暴露于PM(0.5)提取物的二甲基亚砜稀释液中24小时。使用MTT定量活力/增殖，通过酶联免疫吸附测定法检测释放的干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）。所有最高提取物浓度均显著抑制细胞因子产生，但不抑制活力/增殖。一般来说，PM(0.5)提取物对IFN-γ的抑制作用强于对IL-4的抑制作用。基于PM(0.5)的给药质量，所有提取物对IFN-γ产生的抑制作用几乎相同。相反，基于空气体积或吸附在PM(0.5)上的多环芳烃，LPCi提取物对IFN-γ的抑制作用最大。同样，PM(0.5)对IL-4产生的相关影响的排名也因所选参考点（质量或[微克/毫升]或细胞培养中与空气体积[立方米/毫升]相关的粉尘量）的不同而有所差异。基于相应的空气体积，LPCi提取物对IL-4产生的抑制作用最大，而基于浓度的IL-4抑制作用相当。这表明，不仅空气中不同的PM(0.5)质量会产生不同影响，而且PM(0.5)吸附化学物质的差异也会对免疫反应产生不同影响，并导致调节平衡发生变化，这可能对过敏和癌症发展产生影响。
