EFFECTS OF VANADIUM UPON POLYI:C-INDUCED RESPONSES IN RAT LUNG AND ALVEOLAR MACROPHAGES

Author： Cohen Mitchell D. Becker Susanne Devlin Robert Schlesinger Richard B. Zelikoff Judith T.

ISSN： 1087-2620

Source： Journal of Toxicology and Environmental Health, Vol.51, Iss.6, 1997-08, pp. : 591-608

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Abstract

Hosts exposed to vanadium (V) display a subsequent decrease in their resistance to infectious microorganisms. Our earlier studies with rats inhaling occupationally relevant levels of V (as ammonium metavanadate, NH VO ) indicated that several nascent/inducible 4 3 functions of pulmonary macrophages (PAM) were reduced. In the present study, Vexposed rats were examined to determine whether some of the same effects might also occur in situ. Rats were exposed nose-only to air or 2 mg V/m3 (as NH VO ) for 8 h/d 4 3 for 4 d, followed, 24 h later, by intratracheal (it) instillation of polyinosinic:polycytidilic acid (polyI:C) or saline. Analysis of lavaged lung cells/fluids after polyI:C instillation indicated that total lavageable cell/neutrophil numbers and protein levels, while significantly elevated in both exposure groups (as well as in saline-treated V-exposed rats) , were always greater in V-exposed hosts. Exposure to V also affected the inducible production of interleukin 6 (IL-6) and interferon (IFN ), but apparently not that of tumor necrosis factor(TNF ) or IL-1. Although polyI:C induced significant increases in lavage fluid IL-6 and IFN levels in both exposure groups, levels were greater in V-exposed rats. If calculated with respect to total lavaged protein, however, V-exposed rats produced significantly less cytokine. Following polyI:C instillation, there were no marked exposure-related differences in basal or stimulated superoxide anion production by pooled lavaged cells or PAM specifically. With V-exposed rats, pooled cells recovered 24 h after saline instillation displayed reduced production (in both cases) compared to the air control cells; PAM-specific production was affected only after stimulation. In both exposure groups, polyI:C caused decreased superoxide production in recovered cells. Though less apparent with pooled cells, there was a time post polyI:C instillation-dependent decrease in stimulated PAM-specific superoxide production; this effect was greater in PAM from V-exposed rats than in PAM from air controls. Phagocytic activity of PAM from rats in both exposure groups was significantly increased by polyI:C instillation, although total activity in cells obtained from V-exposed rats was always significantly lower compared to air control cells. Our results indicate that short-term, repeated inhalation of occupationally relevant levels of V by rats modulates pulmonary immunocompetence. Modified cytokine production and PAM functionality in response to biological response modifiers (such as lipopolysaccharide, IFN , or polyI:C) may be, at least in part, responsible for the increases in bronchopulmonary disease in humans occupationally exposed to V.