Effect of short-term exogenous pulmonary surfactant treatment on acute lung damage associated with the intratracheal instillation of silica.
The objective of our study was to investigate whether coating the surface of silica with Survanta, a commercially available, bovine pulmonary surfactant, would reduce the in vitro cytotoxicity to alveolar macrophages (AMs), as well as attenuate lung damage in vivo following intratracheal instillation of silica. In the in vitro studies, alveolar macrophages from male Fischer 344 rats were incubated for 1 and 24 h with native or Survanta-treated silica (0.5 mg/ml). At both time points, the native, uncoated silica caused a dramatic loss of AM viability. The AMs were protected, however, when the silica was treated with the Survanta surfactant. This protective effect was significantly greater after 1 h when compared with 24 h. In the in vivo studies, a high dose of silica (10 mg/100 g body weight) was suspended in Survanta and intratracheally instilled into the lungs of male Fischer 344 rats. A number of biochemical and cellular parameters were measured within the bronchoalveolar lavage fluid (BALF) 1 and 14 d after the instillation exposures to assess lung damage. One day after the instillations, the suspension of silica in Survanta resulted in significant reductions in the silica-induced increases in total protein, beta-glucuronidase activity, and influx of neutrophils (PMNs) into the airspaces of the lungs. Fourteen days after the instillation exposures, this protective effect was lost. When Survanta was instilled into the lungs 15 min after the intratracheal instillation of silica, a significant reduction also was demonstrated in the silica-induced elevations in BALF total protein, beta-glucuronidase activity, and influx of PMNs 1 d after the instillation exposures. In an attempt to protect silica-exposed lungs over a longer period of time, Survanta was instilled into the lung 15 min after the silica instillation, and then every other day over a 7-d treatment period. Twenty-four hours after the last Survanta instillation, slight but significant decreases in the silica-induced elevations in BALF total protein and beta-glucuronidase activity were observed. The Survanta treatment, however, had no effect in preventing the infiltration of PMNs into the airspaces of the lungs. The results of this study indicate that artificially coating the silica with surfactant phospholipid offers short-term protection against its toxicity under both in vitro and in vivo conditions.
Antonini
J M
JM
Robert C. Byrd Health Sciences Center, Department of Pharmacology and Toxicology, West Virginia University, Morgantown 26506-9223.
Reasor
M J
MJ
D000704:Analysis of Variance; D000818:Animals; D001688:Biological Products; D001992:Bronchoalveolar Lavage Fluid; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D008168:Lung / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012822:Silicon Dioxide / Q000633:toxicity*; D013997:Time Factors
D001688:Biological Products; D011663:Pulmonary Surfactants; D012822:Silicon Dioxide; C072197:beractant