We have previously demonstrated in alveolar macrophages that aging is associated with a decline in lipopolysaccharide-induced tumor necrosis factor- production. The purpose of the present study was to investigate the immunotoxicological consequences of this defective activation in an experimental model of acute silicosis. Young (3 months old) and old (>18 months old) rats were intratracheally instilled with silica or saline as control. In young animals, as expected, silica induced a significant increase in bronchoalveolar lavage fluid of tumor necrosis factor-, lactate dehydrogenase, and cell numbers, which correlated with increased collagen deposition and silicotic nodule formations. On the contrary, in old rats, no changes in bronchoalveolar lavage fluid or lung parameters were observed, indicating that senescent rats are resistant to the acute effects of silica. These in vivo results were confirmed in vitro, where silica-induced tumor necrosis factor- release was drastically reduced in alveolar macrophages obtained from old animals. This could be explained with a defective protein kinase C II translocation in aged macrophages, due to decreased expression of its anchoring protein RACK-1. Furthermore, a decrease in FAS-L expression and silica-induced apoptosis in old macrophages was observed, supporting the idea that age-associated alterations in signal transduction pathways contribute to decreased sensitivity to silica-induced acute lung fibrosis in old animals.
Resistance to acute silicosis in senescent rats: role of alveolar macrophages / E. Corsini, A. Giani, L. Lucchi, S. Peano, B. Viviani, C. L. Galli, M. Marinovich. - In: CHEMICAL RESEARCH IN TOXICOLOGY. - ISSN 0893-228X. - 16:12(2003), pp. 1520-1527.
|Titolo:||Resistance to acute silicosis in senescent rats: role of alveolar macrophages|
CORSINI, EMANUELA (Primo)
GALLI, CORRADO LODOVICO (Penultimo)
MARINOVICH, MARINA (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2003|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/tx034139+|
|Appare nelle tipologie:||01 - Articolo su periodico|