Kinetics of inflammatory and fibrotic pulmonary changes in a murine model of silicosis

Abstract

A murine model of experimental silicosis has been developed after the intratracheal injection of alpha-quartz crystals. Pulmonary inflammation was monitored by increases in wet lung weight and cell number and protein content of the lung lavage fluid; fibrosis was assessed by measuring increases in hydroxyproline content of the lungs. Acute pulmonary cellular inflammation occurred between weeks 1 and 2, followed by a chronic inflammatory response at week 12. Lung hydroxyproline content, an indication of collagen deposition, was initiated as early as 1 week after silica injection and continued to increase steadily over time. The inflammatory and fibrotic changes induced by silica appeared to be a specific effect of the injection of this toxic particulate and not the result of the introduction of a foreign body, because mice injected with silica crystals were found to have significantly greater increases in acute cellular inflammation and chronic collagen deposition than did mice injected with latex beads. A possible role for the immune system in modulating silica-induced damage was suggested by the variability in response of six different strains of mice (C3H/He, CBA/J, Balb/c, DBA/2, C57BL/6, C57BL/10), which differed at specific genetic loci. Both strains with high (DBA/2) and low (C3H/He) response demonstrated similar patterns of inflammation and fibrosis over a period of 12 weeks. This model demonstrates great potential in future studies for elucidating the role of the immune system in the development of pulmonary inflammation and fibrosis induced by toxic inorganic particulates.