Vanadium-induced chemokine mRNA expression and pulmonary inflammation.

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.