Asbestos fibre length-dependent detachment injury to alveolar epithelial cells in vitro: role of a fibronectin-binding receptor.
A short and a long fibre sample of amosite asbestos were tested for their 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 detachment of the epithelial cells live from their substratum. At the highest dose, on average 28% of the cells present were detached in this way. Studies on the mechanism of the detachment injury showed that it did 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 increase the interaction between fibres and cells, serum and poly-L-lysine, did not influence the detachment injury, nor did lung lining fluid. Conversely, the fibronectin tripeptide RGD alone could cause detachment which suggested that a fibronectin-binding integrin was involved. This receptor could be reduced in activity by long fibre exposure, leading 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 important in the pathology associated with exposure to long fibres.
Institute of Occupational Medicine, Edinburgh, Scotland.
K
K
Donaldson
B G
BG
Miller
E
E
Sara
J
J
Slight
R C
RC
Brown
D001194:Asbestos / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D017639:Asbestos, Amosite; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D011650:Pulmonary Alveoli / Q000378:metabolism*; D017469:Receptors, Fibronectin / Q000502:physiology*
D005353:Fibronectins; D017469:Receptors, Fibronectin; D017639:Asbestos, Amosite; D001194:Asbestos