Crystalline silica (quartz) is Ii well established inflammatory and fibrogenic occupational dust. Past studies have established numerous biochemical mediators of these processes, but the temporal relationships between them have not been determined. To investigate these temporal relationships, rats were exposed to filtered air (control) or silica aerosol of 15mg/m3 (6 hr/day, 5 days/week) and assays were conducted after 5, 10, 16, 20, 30, 41, 79 and 116 days of exposure. Rat lungs were lavaged to isolate bronchoalveolar lavage cells (BALC) and acellular bronchoalveolar lavage fluid (BALF). Pulmonary inflammation was monitored by measuring BALC polymorphonuclear leukocytes (PMN) and alveolar macrophages (AM) differential cell counts. Compared to control, PMN in BA.LC isolated from silica exposed rats were significantly increased after 5 days exposure, remained elevated unti1 41 days, then increased further. BALC AM also were increased in silica-exposed rats, but only after 41 days exposure. Silica cytotoxicity was monitored by analysis of BALF for Lactate dehydrogenase (LDH) and albumin. In silica-exposed rats, both LDH and albumin levels were increased versus control after 5 days exposure, remained relatively constant until day 41, then increased further. AM chemiluminesence, a measure of AM activation and reactive oxygen species production was higher in silica-exposed rats when compared to control. After 41 days of exposure, lung lipid peroxidation was also higher in silica-exposed rats. BALC secretion of TNF-alpha and IL-1, when considered on a per cell basis, was higher in silica-exposed versus control rats by 116 days exposure. Lung fibrosis was confirmed by increased hydroxyproline levels in. the lungs of silica-exposed but not control rats after 116 days exposure. These data indicate that a progressively severe inflammatory reaction occurs in response to inhaled silica and begins to establish the temporal relationships between the various components of the inflammatory response and the development of pulmonary fibrosis.
Animal-studies; Laboratory-animals; Statistical-analysis; Analytical-methods; Analytical-chemistry; Exposure-assessment; Toxicology; Toxins; Toxic-materials; Pulmonary-system-disorders; Pulmonary-disorders; Respiratory-system-disorders; Respiratory-irritants; Particulate-dust; Particulates; Dust-exposure; Dust-inhalation; Dust-particles; Airborne-dusts; Airborne-fibers; Airborne-particles; Silica-dusts; Silicates
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana