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.