ENHANCED RELEASE OF AN ALVEOLAR MACROPHAGE-DERIVED CHEMOATTRACTANT FOR FIBROBLASTS IN RATS AFTER ASBESTOS INHALATION

Our studies indicate the effects of in vivo asbestos exposure on the a bility of alveolar macrophages (AM) to elaborate a chemoattractant for fibroblast using a rat model of asbestos inhalation. Two groups of ra ts were exposed by intermittent inhalation (6 hr/day for 5 days/week o ver a total period of 4 weeks) to either amphibole (crocidolite) or se rpentine (chrysotile) asbestos. A group of control rats were sham-expo sed to clean air only. The animals were sacrificed 2-5 months after th e cessation of exposure. The AM were obtained from the 3 exposure grou ps in 2 different rat strains by the bronchoalveolar lavage and the cu ltured in RPMI-1640 medium for 24-96 hr at 37-degrees-C. The supernata nts from cultured AM were tested for chemotactic activity towards feta l rat skin fibroblasts in a chemotactic assay using 8 mum pore-size fi lters. The culture supernatants of AM obtained from crocidolite-expose d rats exhibited a significantly greater chemotactic activity towards rat fibroblasts than similar culture supernatants from sham-exposed co ntrol animals (p<0.01) in both rat strains. Significant chemotactic ac tivity was observed after chrysotile exposure (p<0.05) in ACI rats but not in Fischer-344 rats. Maximal chemoattractant release from AM was noted after 48 hr in culture. Preliminary characterization of the chem oattractant has shown that it is a thermolabile and trypsin sensitive factor whose activity was partially reduced after dialysis. Since AM a ccumulate at sites of intrapulmonary asbestos deposition, these findin gs may have relevance to the pathologic accumulation of interstitial l ung fibroblasts which occurs during asbestos-mediated lung injury.