title: Effects of vanadium upon polyl:C-induced responses in rat lung and alveolar macrophages.
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, NH4VO3) indicated that several nascent/inducible functions of pulmonary macrophages (PAM) were reduced. In the present study, V-exposed 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 NH4VO3) for 8 h/d for 4 d, followed, 24 h later, by intratracheal (it) instillation of polyinosinic:polycytidilic acid (polyl:C) or saline. Analysis of lavaged lung cells/fluids after polyl: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 gamma (IFN gamma), but apparently not that of tumor necrosis factor-alpha (TNF alpha) or IL-1. Although polyl:C induced significant increases in lavage fluid IL-6 and IFN gamma 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 polyl: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, polyl:C caused decreased superoxide production in recovered cells. Though less apparent with pooled cells, there was a time post polyl: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 polyl: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 gamma, or polyl:C) may be, at least in part, responsible for the increases in bronchopulmonary disease in humans occupationally exposed to V.
authors.affiliation: Nelson Institute of Environmental Medicine, New York University Medical Center, New York 10987, USA. cohenm@charlotte.med.nyu.edu
authors.forename: M D
authors.initials: MD
authors.lastname: Cohen
authors.forename: S
authors.initials: S
authors.lastname: Becker
authors.forename: R
authors.initials: R
authors.lastname: Devlin
authors.forename: R B
authors.initials: RB
authors.lastname: Schlesinger
authors.forename: J T
authors.initials: JT
authors.lastname: Zelikoff
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D007369:Interferon Inducers / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010587:Phagocytosis; D011070:Poly I-C / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species; D013047:Specific Pathogen-Free Organisms; D013481:Superoxides / Q000378:metabolism; D014638:Vanadates / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D007369:Interferon Inducers; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D013481:Superoxides; D014638:Vanadates; D007371:Interferon-gamma; C101036:ammonium metavanadate; D011070:Poly I-C