Imrich A, Ning Y, Kobzik L
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, 02115, USA.
Toxicol Appl Pharmacol. 2000 Sep 1;167(2):140-50. doi: 10.1006/taap.2000.9002.
We sought to characterize the bioactive constituents of concentrated ambient air particles (CAPs) through correlation of alveolar macrophage (AM) biological responses (production of TNF, macrophage inflammatory protein (MIP-2), nitrite; cell viability) to components of particle samples. CAPs samples collected on different days showed a range of bioactivity and a strong correlation was found between AM cytokine release and increased AM light scatter, a flow cytometric measure of relative particle load. Evaluation of soluble and insoluble fractions of CAPs suspensions indicate that 1) most biological effects on AMs are mediated by insoluble components and certain particle adsorbed factors such as endotoxin; 2) the variable bioactivity of CAPs collected on different days arises primarily from differences in the relative proportion of insoluble and soluble mass present in particle suspensions; and 3) the activation state of the AM influences which insoluble components are most bioactive. Use of endotoxin neutralizing agents (e.g., polymyxin-B) showed particle-adsorbed endotoxin in CAPs suspensions causes activation of normal (control) AMs while other (nonendotoxin) components are predominantly responsible for the enhanced cytokine release observed by primed AMs incubated with CAPs. The AM biological response did not correlate with any of a panel of elements quantified within insoluble CAPs samples (Al, Cd, Cr, Cu, Fe, Mg, Mn, Ni, S, Ti, V). These data demonstrate an important role for cell activation and phagocytosis of insoluble particulate matter in the response of AMs to CAPs suspensions.
我们试图通过将肺泡巨噬细胞（AM）的生物学反应（肿瘤坏死因子、巨噬细胞炎性蛋白（MIP-2）、亚硝酸盐的产生；细胞活力）与颗粒样品的成分进行关联，来表征浓缩环境空气颗粒（CAPs）的生物活性成分。在不同日期收集的CAPs样品表现出一系列生物活性，并且发现AM细胞因子释放与AM光散射增加之间存在很强的相关性，AM光散射是相对颗粒负荷的流式细胞术测量指标。对CAPs悬浮液的可溶和不可溶部分的评估表明：1）对AMs的大多数生物学效应是由不可溶成分和某些颗粒吸附因子（如内毒素）介导的；2）不同日期收集的CAPs的可变生物活性主要源于颗粒悬浮液中不可溶和可溶物质相对比例的差异；3）AMs的激活状态影响哪些不可溶成分最具生物活性。使用内毒素中和剂（如多粘菌素B）表明，CAPs悬浮液中颗粒吸附的内毒素会激活正常（对照）AMs，而其他（非内毒素）成分主要负责与CAPs孵育的致敏AMs所观察到的细胞因子释放增强。AM生物学反应与不可溶CAPs样品中定量的一组元素（铝、镉、铬、铜、铁、镁、锰、镍、硫、钛、钒）中的任何一种均无相关性。这些数据证明了细胞激活和吞噬不可溶颗粒物在AMs对CAPs悬浮液反应中的重要作用。
