VANADIUM-INDUCED CHEMOKINE MESSENGER-RNA EXPRESSION AND PULMONARY INFLAMMATION

Occupational exposure to vanadium is common in petrochemical, mining, steel, and utilities industries and results in toxic effects largely c onfined to the respiratory system. Vanadium exposure has been associat ed with inflammatory changes in the upper and lower respiratory tracts in addition to changes in pulmonary function. We investigated the abi lities of several vanadium compounds to increase mRNA levels for selec ted cytokines in bronchoalveolar lavage (BAL) cells and also to induce pulmonary inflammation. Rats (200-250 g) were intratracheally instill ed with either sodium metavanadate (NaVO3), vanadyl sulfate (VOSO4), v anadium pentoxide (V2O5) at several concentrations, or vehicle alone. Pulmonary inflammation was assessed by cytologic analysis of cells rec overed from the respiratory tract (1 hr to 10 days postexposure). All three vanadium compounds were capable of inducing pulmonary inflammati on in a dose-dependent manner, Neutrophil influx was greatest followin g exposure to VOSO4 (peaked at approximately 40% of cell population) a nd lowest following exposure to V2O5 (peaked at approximately 20%). Si gnificant neutrophil influx was detected as early as 4 hr following th e instillation of NaVO3 and VOSO4 but not until 24 hr upon exposure to V2O5, The VOSO4-induced inflammatory response persisted longer (5 day s) than that induced by NaVO3 and V2O5, Analysis of inflammatory cytok ine mRNA expression closely followed these cytologic observations. Lev els of mRNA for macrophage inflammatory protein-2 (MIP-2) and KC, cons idered the principal neutrophil chemotactic factors expressed in the r at, were rapidly induced as early as 1 hr following exposure, continue d to be expressed throughout 48 hr, and were low but detectable at 5 a nd 10 days. NaVO3 and VOSO4, both very soluble forms of vanadium, tend ed to induce pulmonary inflammation and inflammatory cytokine mRNA exp ression more rapidly and more intensely than the less soluble form, V2 O5 Analysis of KC mRNA expression in BAL cells 24 hr after instillatio n of NaVO3 by PCR in situ hybridization confirmed the increase in KC m RNA levels and indicated that alveolar macrophages have the highest ex pression 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 e xpression of MIP-2 and KC mRNA in BAL cells prior to the observed neut rophilia implicate them as important in the initiation of inflammation . (C) 1996 Academic Press, Inc.