Pierce L M, Alessandrini F, Godleski J J, Paulauskis J D
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Toxicol Appl Pharmacol. 1996 May;138(1):1-11. doi: 10.1006/taap.1996.9999.
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.
在石油化工、采矿、钢铁和公用事业等行业中，职业性接触钒很常见，其毒性作用主要局限于呼吸系统。除了肺功能变化外，钒暴露还与上、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）细胞中特定细胞因子mRNA水平以及诱导肺部炎症的能力。将体重200 - 250克的大鼠经气管内分别滴注几种浓度的偏钒酸钠（NaVO3）、硫酸氧钒（VOSO4）、五氧化二钒（V2O5）或仅滴注赋形剂。通过对呼吸道回收细胞（暴露后1小时至10天）进行细胞学分析来评估肺部炎症。所有三种钒化合物均能够以剂量依赖的方式诱导肺部炎症。暴露于VOSO4后中性粒细胞流入最多（峰值约为细胞总数的40%），暴露于V2O5后最少（峰值约为20%）。早在滴注NaVO3和VOSO4后4小时就检测到显著的中性粒细胞流入，但暴露于V2O5后直到24小时才检测到。VOSO4诱导的炎症反应持续时间比NaVO3和V2O5诱导的更长（5天）。炎症细胞因子mRNA表达分析与这些细胞学观察结果密切相关。巨噬细胞炎性蛋白 - 2（MIP - 2）和KC的mRNA水平，被认为是大鼠中主要的中性粒细胞趋化因子，早在暴露后1小时就迅速诱导，在48小时内持续表达，在5天和10天时较低但仍可检测到。NaVO3和VOSO4这两种钒的非常易溶形式，比难溶形式V2O5更倾向于更快、更强烈地诱导肺部炎症和炎症细胞因子mRNA表达。通过原位杂交PCR分析滴注NaVO3后24小时BAL细胞中KC mRNA表达，证实了KC mRNA水平的增加，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该金属从肺表面快速清除，并在BAL细胞和肺组织中大量积累。在观察到中性粒细胞增多之前，BAL细胞中MIP - 2和KC mRNA的快速表达表明它们在炎症起始中很重要。
