ASBESTOS FIBER LENGTH-DEPENDENT DETACHMENT INJURY TO ALVEOLAR EPITHELIAL-CELLS INVITRO - ROLE OF A FIBRONECTIN-BINDING RECEPTOR

A short and a long fibre sample of amosite asbestos were tested for th eir effects on cells of the human Type 2 alveolar epithelial cell-line A549 in vitro. The long amosite sample was found to cause a rapid det achment of the epithelial cells live from their substratum. At the hig hest dose, on average 28% of the cells present were detached in this w ay. Studies on the mechanism of the detachment injury showed that it d id not involve oxidants since it was not ameliorated by scavengers of active oxygen species. Neither was the effect reduced by treatment of the fibres with the iron chelator Desferal. Treatments reported to inc rease the interaction between fibres and cells, serum and poly-L-lysin e, did not influence the detachment injury, nor did lung lining fluid. Conversely, the fibronectin tripeptide RGD alone could cause detachme nt which suggested that a fibronectin-binding integrin was involved. T his receptor could be reduced in activity by long fibre exposure, lead ing to detachment. The detaching effect of fibre could be mimicked by the protein kinase C activator PMA, and so the second messenger system of the cell could also be involved. This type of injury could be impo rtant in the pathology associated with exposure to long fibres.