Vanadium-induced chemokine mRNA expression and pulmonary inflammation.
Vanadium-induced chemokine mRNA expression and pulmonary inflammation.
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DOI：
10.1006/taap.1996.9999
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发表时间：
1996-05
影响因子：
3.8
通讯作者：
Lisa Pierce;F. Alessandrini;J. Godleski;J. Paulauskis
中科院分区：
文献类型：
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作者：
Lisa Pierce;F. Alessandrini;J. Godleski;J. Paulauskis
钒的职业暴露在石油化工、采矿、钢铁和公用事业行业中很常见，其毒性作用主要局限于呼吸系统。除了肺功能的变化外，暴露于万古霉素还与上呼吸道和下呼吸道的炎症变化有关。我们研究了几种钒化合物增加支气管肺泡灌洗（BAL）细胞中选定细胞因子的mRNA水平以及诱导肺部炎症的能力。向大鼠（200-250 g）气管内滴注几种浓度的偏钒酸钠（NaVO 3）、硫酸氧钒（VOSO 4）、五氧化二钒（V2 O 5）或单独的溶媒。通过从呼吸道回收的细胞的细胞学分析评估肺部炎症（暴露后1小时至10天）。所有三种钒化合物都能够以剂量依赖性方式诱导肺部炎症。暴露于VOSO 4后，神经元内流最大（峰值约为细胞群的40%），暴露于V2 O 5后最低（峰值约为20%）。显著的中性粒细胞内流检测到早在4小时后滴注的NaVO 3和VOSO 4，但直到24小时后，暴露于V2 O 5。VOSO 4诱导的炎症反应持续时间（5天）比NaVO 3和V2 O 5诱导。炎性细胞因子mRNA表达的分析密切关注这些细胞学观察结果。巨噬细胞炎性蛋白-2（MIP-2）和KC（被认为是大鼠中表达的主要中性粒细胞趋化因子）的mRNA水平早在暴露后1小时即被迅速诱导，在整个48小时内持续表达，并且在5天和10天时较低但可检测到。NaVO 3和VOSO 4，这两种非常可溶的钒形式，倾向于诱导肺部炎症和炎性细胞因子mRNA的表达更快，更强烈的溶解度较低的形式，V2 O 5。通过PCR原位杂交分析滴注NaVO 3后24小时BAL细胞中KC mRNA表达证实KC mRNA水平增加，并表明肺泡巨噬细胞具有观察到的最高表达水平。灌洗液、BAL细胞和肺中的钒含量表明金属从肺表面快速清除，并在BAL细胞和肺组织中大量蓄积。MIP-2和KC mRNA在BAL细胞中的快速表达在所观察到的嗜中性粒细胞之前暗示它们在炎症的起始中是重要的。
Occupational exposure to vanadium is common in petrochemical, mining, steel, and utilities industries and results in toxic effects largely confined to the respiratory system. Vanadium exposure has been associated with inflammatory changes in the upper and lower respiratory tracts in addition to changes in pulmonary function. We investigated the abilities of several vanadium compounds to increase mRNA levels for selected cytokines in bronchoalveolar lavage (BAL) cells and also to induce pulmonary inflammation. Rats (200-250 g) were intratracheally instilled with either sodium metavanadate (NaVO3), vanadyl sulfate (VOSO4), vanadium pentoxide (V2O5) at several concentrations, or vehicle alone. Pulmonary inflammation was assessed by cytologic analysis of cells recovered from the respiratory tract (1 hr to 10 days postexposure). All three vanadium compounds were capable of inducing pulmonary inflammation in a dose-dependent manner. Neutrophil influx was greatest following exposure to VOSO4 (peaked at approximately 40% of cell population) and lowest following exposure to V2O5 (peaked at approximately 20 %). Significant neutrophil influx was detected as early as 4 hr following the instillation of NaVO3 and VOSO4 but not until 24 hr upon exposure to V2O5. The VOSO4-induced inflammatory response persisted longer (5 days) than that induced by NaVO3 and V2O5. Analysis of inflammatory cytokine mRNA expression closely followed these cytologic observations. Levels of mRNA for macrophage inflammatory protein-2 (MIP-2) and KC, considered the principal neutrophil chemotactic factors expressed in the rat, were rapidly induced as early as 1 hr following exposure, continued to be expressed throughout 48 hr, and were low but detectable at 5 and 10 days. NaVO3 and VOSO4, both very soluble forms of vanadium, tended to induce pulmonary inflammation and inflammatory cytokine mRNA expression more rapidly and more intensely than the less soluble form, V2O5. Analysis of KC mRNA expression in BAL cells 24 hr after instillation of NaVO3 by PCR in situ hybridization confirmed the increase in KC mRNA levels and indicated that alveolar macrophages have the highest expression level observed. Vanadium content of lavage fluid, BAL cells, and lung indicated rapid clearance of the metal from the lung surface and substantial accumulation by BAL cells and lung tissue. The rapid expression of MIP-2 and KC mRNA in BAL cells prior to the observed neutrophilia implicate them as important in the initiation of inflammation.