Effects of diesel exhaust particles (DEP), carbon black, and silica on macrophage responses to lipopolysaccharide: Evidence of DEP suppression of macrophage activity
Effects of diesel exhaust particles (DEP), carbon black, and silica on macrophage responses to lipopolysaccharide: Evidence of DEP suppression of macrophage activity
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DOI：
10.1080/009841099157232
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发表时间：
1999-11-12
期刊：
影响因子：
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通讯作者：
Ma, JYC
中科院分区：
文献类型：
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作者：
Yang, HM;Barger, MW;Ma, JYC
通过监测柴油机尾气颗粒（DEP）刺激的白细胞间素-1 （IL-1）和肿瘤坏死因子- α (tnf - α)的产生，研究了柴油机尾气颗粒（DEP）暴露对肺泡巨噬细胞（AM）对体内和体外脂多糖（LPS）攻击的影响。通过将DEP引起的肺反应与炭黑（一种几乎没有吸附有机化合物的碳质颗粒）或二氧化硅（一种已知的肺毒性粉尘）的肺反应进行比较，评估了DEP的不溶性颗粒和有机化合物在改变肺反应中的作用。雄性Sprague-Dawley大鼠被暴露于单次气管内剂量（5或35 mg/kg体重）DEP、CB或二氧化硅，或生理盐水。暴露后1、3、7 d处死小鼠。为了研究对细菌产物LPS的反应性，将颗粒暴露大鼠分离的AM体外注射LPS (0.1 μ g/10(6) AM)，并监测LPS刺激的细胞因子释放。此外，大鼠气管内暴露于单剂量DEP (5 mg/kg)， 3天后在体内暴露于1 mg/kg LPS 3小时，然后通过AM测量细胞因子的产生。DEP暴露导致支气管肺泡灌洗液中中性粒细胞浸润和白蛋白和乳酸脱氢酶（LDH）活性水平升高；这些反应与接触黑炭黑或二氧化硅引起的反应没有本质上的不同。暴露于deep的大鼠的AM显示自发产生IL-1增加，但不增加tnf - α，而CB或二氧化硅则相反。在体外LPS刺激下，与DEP和LPS作用的总和相比，暴露于DEP的大鼠的AM显示出tnf - α分泌的显著减少，IL-1分泌的减少程度较小。相比之下，暴露于炭黑或二氧化硅的大鼠的AM对随后的LPS攻击没有表现出这种降低的反应性。DEP对LPS刺激的AM产生IL-1和tnf - α的抑制作用进一步被暴露于DEP和LPS的大鼠体内的结果所证实。综上所述，这些结果表明，尽管DEP、CB和二氧化硅都能在颗粒刺激下诱导肺部炎症反应，但只有DEP在LPS刺激下抑制AM细胞因子的释放。相对于DEP和CB暴露，不同的细胞反应可能是由于DEP上吸附的有机化合物的存在，这可能导致DEP暴露后宿主对肺部感染的易感性增加。
The effects of diesel exhaust particle (DEP) exposure on alveolar macrophage (AM) response to ex vivo and in vivo lipopolysaccharide (LPS) challenge were determined by monitoring LPS-stimulated production of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). The roles of the insoluble particulate and the organic compounds of DEP in altering pulmonary responses were evaluated by comparing the DEP-induced pulmonary responses to those of carbon black (CB), a carbonaceous particle with few adsorbed organic compounds, or to silica, a known pneumotoxic dust. Male Sprague-Dawley rats were exposed to a single intratracheal dose (5 or 35 mg/kg body weight) of DEP, CB, or silica, or to saline vehicle. Ran were sacrificed 1, 3, or 7 d postexposure. To study the responsiveness to the bacterial product LPS, AM isolated from particle-exposed rats were challenged ex vivo with LPS (0.1 mu g/10(6) AM) and LPS-stimulated cytokine release was monitored. In addition, rats were exposed intratracheally to a single dose of DEP (5 mg/kg) and 3 d later exposed in vivo to 1 mg/kg LPS for 3 h prior to measurement of cytokine production by AM. DEP exposure resulted in neutrophil infiltration and elevated levels of albumin and lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid; these responses were not substantially different from those elicited by CB or silica exposure. AM from DEP-exposed rats showed increased spontaneous production of IL-1, but not TNF-alpha, while the opposite was true for CB or silica. Upon ex vivo challenge with LPS, AM from DEP-exposed rats showed a significant decrease in the secretion of TNF-alpha and, to a lesser extent, IL-1, compared to the sum of the DEP and LPS effects. In contrast, AM from CB- or silica-exposed rats did not show this decreased responsiveness to subsequent LPS challenge. This inhibitory action of DEP on LPS-stimulated AM production of IL-1 and TNF-alpha was further confirmed by the results obtained from rats exposed to both DEP and LPS in vivo. in summary, these results indicate that while DEP, CB, and silica all induce pulmonary inflammatory responses due to particle stimulation, only DEP suppress AM cytokine release in response to LPS stimulation. The contrasting cellular response with respect to DEP and CB exposures may be due to the presence of adsorbed organic compounds on DEP, which may contribute to the increased susceptibility of hosts to pulmonary infections after DEP exposure.