A study of macrophage-mediated initiation of fibrosis by asbestos and silica using a diffusion chamber technique.

Several cellular interactions have been identified as potentially important in fibrogenesis induced by mineral dusts. Evaluation of their relative importance in vivo remains a problem. Sealed diffusion chambers limited by Nuclepore membranes and implanted into mouse peritoneal cavities provide a means of assessing different stages of fibrogenesis by separating initiating mechanisms (dust-macrophage-lymphocyte combinations inside the chamber) from the target tissue. Fibrous reactions surrounding the chambers were quantitated by macroscopic and histological scoring, and by measurement of 14C glycine incorporated at the reaction site. Using this model the fibrogenicity of Rhodesian A chrysotile asbestos, DQ12 quartz and haematite were compared. Whereas asbestos-macrophage ratios of between 6 . 6 and 900 micrograms/10(6) mouse peritoneal macrophages (MPM) produced fibrosis, an equivalent response was obtained with 0.05 micrograms silica/10(6) MPM. Silica in amounts greater than this produced macrophage cytotoxicity without fibrogenesis. Haematite-macrophage combinations produced no significant fibrosis. It was confirmed that a direct dust-macrophage interaction forms the essential first step in fibrogenesis by both asbestos and silica and that the fibrogenicity is mediated by diffusible factor(s). Prior stimulation of host mice with Freund's complete adjuvant modified the fibrogenic response to some dust-cell combinations, suggesting an important role for host responses in determining the outcome of fibrogenic stimuli.