title: Enhancement of nitric oxide production by pulmonary cells following silica exposure.
abstract: In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. In vitro exposure of AM to silica does not stimulate .NO production or enhance iNOS message. However, treatment of naive AM with conditioned media from BALC harvested from silica-exposed rats does increase iNOS message and .NO production by these AM. The potency of this conditioned medium is dependent on interaction between AM and PMN. In the rat model, a relationship exists between the ability of various dusts to cause PMN recruitment or protein leakage into the alveolar space and the induction of iNOS message in BALC, i.e., silica > coal mine dust > carbonyl iron > titanium dioxide. Similarly, a comparison of BALC from a healthy volunteer, a silica-exposed coal miner with a normal chest radiograph, and a silica-exposed coal miner with an abnormal chest radiograph shows a correlation between pathology and both the level of iNOS message in BALC and the magnitude of .NO-dependent CL from AM. These data suggest that .NO may play a role in silicosis and that human pulmonary phagocytes exhibit enhanced .NO production in response to an inflammatory insult.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. vic1@cdc.gov
authors.forename: V
authors.initials: V
authors.lastname: Castranova
authors.forename: L J
authors.initials: LJ
authors.lastname: Huffman
authors.forename: D J
authors.initials: DJ
authors.lastname: Judy
authors.forename: J E
authors.initials: JE
authors.lastname: Bylander
authors.forename: L N
authors.initials: LN
authors.lastname: Lapp
authors.forename: S L
authors.initials: SL
authors.lastname: Weber
authors.forename: J A
authors.initials: JA
authors.lastname: Blackford
authors.forename: R D
authors.initials: RD
authors.lastname: Dey
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003032:Coal Mining; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D016273:Occupational Exposure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000633:toxicity*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D009569:Nitric Oxide; D012822:Silicon Dioxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat