PMID- 9242230 OWN - NLM STAT- MEDLINE DCOM- 19970821 LR - 20171116 IS - 0098-4108 (Print) IS - 0098-4108 (Linking) VI - 51 IP - 6 DP - 1997 Aug 29 TI - Effects of vanadium upon polyl:C-induced responses in rat lung and alveolar macrophages. PG - 591-608 AB - 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. FAU - Cohen, M D AU - Cohen MD AD - Nelson Institute of Environmental Medicine, New York University Medical Center, New York 10987, USA. cohenm@charlotte.med.nyu.edu FAU - Becker, S AU - Becker S FAU - Devlin, R AU - Devlin R FAU - Schlesinger, R B AU - Schlesinger RB FAU - Zelikoff, J T AU - Zelikoff JT LA - eng GR - ES00260/ES/NIEHS NIH HHS/United States GR - OH03064-01/OH/NIOSH CDC HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Toxicol Environ Health JT - Journal of toxicology and environmental health JID - 7513622 RN - 0 (Interferon Inducers) RN - 0 (Interleukin-6) RN - 0 (Reactive Oxygen Species) RN - 11062-77-4 (Superoxides) RN - 3WHH0066W5 (Vanadates) RN - 82115-62-6 (Interferon-gamma) RN - FL85PX638G (ammonium metavanadate) RN - O84C90HH2L (Poly I-C) SB - IM MH - Administration, Inhalation MH - Animals MH - Bronchoalveolar Lavage Fluid/cytology MH - Cells, Cultured MH - Interferon Inducers/*pharmacology MH - Interferon-gamma/biosynthesis MH - Interleukin-6/biosynthesis MH - Lung/drug effects/*metabolism MH - Macrophages, Alveolar/drug effects/*metabolism MH - Male MH - Phagocytosis MH - Poly I-C/*pharmacology MH - Rats MH - Rats, Inbred F344 MH - Reactive Oxygen Species MH - Specific Pathogen-Free Organisms MH - Superoxides/metabolism MH - Vanadates/administration & dosage/*toxicity EDAT- 1997/08/29 00:00 MHDA- 1997/08/29 00:01 CRDT- 1997/08/29 00:00 PHST- 1997/08/29 00:00 [pubmed] PHST- 1997/08/29 00:01 [medline] PHST- 1997/08/29 00:00 [entrez] AID - 10.1080/00984109708984046 [doi] PST - ppublish SO - J Toxicol Environ Health. 1997 Aug 29;51(6):591-608. doi: 10.1080/00984109708984046.