VITRONECTIN ENHANCES INTERNALIZATION OF CROCIDOLITE ASBESTOS BY RABBIT PLEURAL MESOTHELIAL CELLS VIA THE INTEGRIN ALPHA-V-BETA-5

The mechanism by which pleural mesothelial cells, the likely progenito r cells of asbestos-induced mesothelioma, recognize and internalize cr ocidolite asbestos is unknown. Because incubation of asbestos fibers w ith serum increases their association with cells, we asked whether a p rotein coat on asbestos increased internalization of fibers via specif ic cellular receptors, Coating crocidolite with vitronectin, but not w ith fibronectin or other proteins, increased fiber internalization by rabbit pleural mesothelial cells, as measured by a new technique using fluorescence confocal microscopy. Receptors for vitronectin, alpha v beta 3 and alpha v beta 5, were identified on mesothelial cells. Inhib iting vitronectin receptors by plating cells on a vitronectin substrat e or incubating cells with excess soluble vitronectin reduced internal ization of vitronectin-coated crocidolite, Inhibition of alpha v beta 5, but not alpha v beta 3, with blocking antibodies similarly reduced internalization. In addition, alpha v beta 5, but not alpha v beta 3, showed immunocytochemical colocalization with fibers. Of biologic rele vance, coating crocidolite with serum also increased internalization v ia alpha v beta 5, an effect dependent on the vitronectin in serum. We conclude that pleural mesothelial cells recognize and internalize vit ronectin- and serum-coated asbestos via the integrin alpha v beta 5. S ince integrins initiate some of the same signaling pathways as does as bestos, our findings may provide insights into the mechanisms of asbes tos-induced biologic effects.