Asbestos exposure enhances the release of fibroblast growth factor by sheep alveolar macrophages

Interaction between free airway cells (FAC) and lung fibroblasts was studied in a sheep model of asbestosis. Three groups of six sheep each received, respectively, by repeated intratracheal instillations, saline (control), 328 mg (low dose), and 2282 mg (high dose) of UICC chrysotile B asbestos. Sixteen months after the first instillation, FAC obtained by segmental bronchoalveolar lavage (BAL) of sheep in each group were incubated for various intervals, and the effect of their culture supernatants (FAC-SN) on human embryonic lung fibroblast proliferation was determined. FAC-SN from control animals stimulated thymidine (3H-TdR) incorporation by lung fibroblasts two- to threefold compared to untreated cultures. Maximal stimulation was observed at 48 hr and was correlated with a significant increase of the fibroblast population at 72 hr. FAC population from control sheep consisted primarily of macrophages (79%) and lymphocytes (15%), and separation of these two cell populations indicated that only macrophages produced the fibroblast-stimulating activity. Production occurred within 1 hr of incubation and was maximal between 2 and 4 hr. This activity was nondialyzable and stable at 56 degrees C for 30 min, but was destroyed at 80 degrees C and low pH. Moreover, FAC-SN from sheep exposed to asbestos stimulated 3H-TdR incorporation by fibroblasts five- to sixfold compared to two- to threefold for control FAC-SN. This activity may modulate fibrogenesis and may be involved in the eventual fibrogenic response to asbestos.