ENHANCEMENT OF NITRIC-OXIDE PRODUCTION BY PULMONARY CELLS FOLLOWING SILICA EXPOSURE

In vivo exposure of rat lungs to crystalline silica either by intratra cheal instillation or by inhalation results in an increase in mRNA lev els for inducible nitric oxide synthase (iNOS) in bronchoalveolar lava ge cells (BALC), elevated nitric oxide ((NO)-N-.) production by BALC, and an increase in (NO)-N-.-dependent chemiluminescence (CL) from alve olar macrophages (AM). induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lung s but is not significantly elevated in lavaged lung tissue. in vitro e xposure of AM to silica does not stimulate (NO)-N-. production or enha nce iNOS message. However, treatment of naive AM with conditioned medi a from BALC harvested from silica-exposed rats does increase iNOS mess age and (NO)-N-. production by these AM. The potency of this condition ed medium is dependent on interaction between AM and PMN. In the rat m odel, a relationship exists between the ability of various dusts to ca use PMN recruitment or protein leakage into the alveolar space and the induction of iNOS message in BALC, i.e., silica > coal mine dust > ca rbonyl iron > titanium dioxide. Similarly, a comparison of BALC from a healthy volunteer, a silica-exposed coal miner with a normal chest ra diograph, and a silica-exposed coal miner with an abnormal chest radio graph shows a correlation between pathology and both the level of iNOS message in BALC and the magnitude of (NO)-N-.-dependent CL from AM. T hese data suggest that (NO)-N-. may play a role in silicosis and that human pulmonary phagocytes exhibit enhanced (NO)-N-. production in res ponse to an inflammatory insult.