CHARACTERIZATION OF THE BRONCHOALVEOLAR CELLULAR-RESPONSE IN EXPERIMENTAL ASBESTOSIS - DIFFERENT REACTIONS DEPENDING ON THE FIBROGENIC POTENTIAL

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Abstract
Analysis of bronchoalveolar cell types and structure was performed during the development of asbestos-induced lung injury in the rat. Animals received single intratracheal injections of one of the following: saline (control), UICC, chrysotile B asbestos (5 mg) or very short 4T30 chrysotile fibers (5 mg). Bronchoalveolar lavage (BAL) was performed at various intervals after instillation. Analysis of BAL fluid showed a significant increase in inflammatory cells in response to asbestos; this persisted longer in animals treated with chrysotile B. Presence of numerous mitotic figures in BAL fluid of treated animals suggests that macrophage replication may contribute in part to this response. Differential cellular analysis indicated that after injection of long chrysotile fibers, which causes fibrotic lesions within 7 days, polymorphonuclear leukocytes (PMN) appear as early as day 1 in significant concentration (40%) in the bronchoalveolar compartment, and they persist through day 7 after treatment. From day 7 to day 21, multinucleated cells (MGC) were found in lavage fluid (5-8%). Most of these cells were binucleated, and none had > 3 nuclei. By contrast, exposure to very short chrysotile fibers caused only a very transient influx of PMN on day 1. By day 7, there was a significant increase in MGC, which persisted through day 21, at which time no fibrosis was apparent. Although most of these cells were binucleated, many cells had 3 or more nuclei. The giant cells were predominantly of the foreign body type, with MGC of the Langhans type also present. In this rat model, lung alveolitis and fibrosis apparently are associated with different bronchoalveolar cellular reactions, and they raise the question of a possible role for PMN and MGC in modulating macrophage function and lung response to injury.