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 surf ace of silica with Survanta, a commercially available, bovine pulmonar y surfactant, would reduce the in vitro cytotoxicity to alveolar macro phages (AMs), as well as attenuate lung damage in vivo following intra tracheal instillation of silica. In the in vitro studies, alveolar mac rophages 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, t he native, uncoated silica caused a dramatic loss of AM viability. The AMs were protected, however, when the silica was treated with the Sur vanta surfactant. This protective effect was significantly greater aft er 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 intrat racheally instilled into the lungs of male Fischer 344 rats. A number of biochemical and cellular parameters were measured within the bronch oalveolar lavage fluid (BALF) 1 and 14 d after the instillation exposu res to assess lung damage. One day after the instillations, the suspen sion of silica in Survanta resulted in significant reductions in the s ilica-induced increases in total protein, beta-glucuronidase activity, and influx of neutrophils (PMNs) into the airspaces of the lungs. Fou rteen days after the instillation exposures, this protective effect wa s lost When Survanta was instilled into the lungs 15 min after the int ratracheal instillation of silica, a significant reduction also was de monstrated in the silica-induced elevations in BALF total protein, and glucuronidase activity, and influx of PMNs 1 d after the instillation exposures. In an attempt to protect silica-exposed lungs over a longe r period of rime, Survanta was instilled into the lungs 15 min after t he 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 to tal protein and beta-glucuronidase activity were observed. The Survant a treatment however, had no effect in preventing the infiltration of P MNs into the airspaces of the lungs. The results of this study indicat e that artificially coating the silica with surfactant phospholipid of fers short-term protection against its toxicity under both in vitro an d in vivo conditions.